Light can kill the photoreceptors of the eye, not only very bright direct sunlight, but more moderate illumination if the light is present continuously. Recent experiments show that rod apoptosis can be triggered by strong and constant activation of transduction, and that death can be prevented if transduction is inhibited even though the eye is illuminated. Vitamin A deficiency and genetically inherited diseases, such as some forms of retinitis pigmentosa and Leber congenital amaurosis, appear to kill like this: transduction (...) is activated at a high rate and continuously, and this causes the rods to die. Why does transduction kill? Our best guess is that continuous activation produces a prolonged lowering of the Ca2+ concentration, which is also thought to kill neurons in tissue culture and during the development of the nervous system. To prevent death in constant light, rods have evolved protective mechanisms including modulation of channels and ion transport to keep the Ca2+ from going too low. Prolonged light exposure also causes migration of transduction proteins from one part of the cell to another and a reversible shortening of the rod outer segments, the part of the cell that contains the pigment rhodopsin. All of these mechanisms are at work in the normal eye to reduce transduction and prevent the Ca2+ concentration from dropping too low for too long a time. That most of us retain our vision our entire lives is a testament to their effectiveness. BioEssays 28: 344–354, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Genetic abnormalities of three factors related to the photoreceptor mechanism have been reported in both animal models and humans. Apoptotic mechanism has also been suggested as a final common pathway of photoreceptor cell death. Our findings of increased level of glutamate in photoreceptor cells in rds mice suggest that amino acid might mediate between these two pathological mechanisms.

This commentary discusses the balance of phosphodiesterase and guanylate cyclase activities in vertebrate photoreceptors at moderate light intensities. The rate of cGMP hydrolysis and synthesis seem to equal each other. Ca2+as regulator of both enzyme activities is also effectively buffered in photoreceptor cells by cytoplasmic buffer components.

The mutations that cause many forms of inherited retinal degenerations have been identified, yet the mechanisms by which these mutations lead to death of photoreceptor cells of the retina are not completely understood. Investigations of the pathways from mutation to retinal degeneration have focused on spontaneous and engineered animal models of disease. Based on the studies performed to date, four major categories of degeneration mechanism can be identified. These include disruption of photoreceptor outer segment morphogenesis, metabolic overload, dysfunction of retinal (...) pigment epithelial cells, and chronic activation of phototransduction. Future investigations will likely identify additional mechanisms of photoreceptor damage. This review will summarize what has been learned from studying animal models of non-syndromic inherited retinal degenerations. BioEssays 23:605–618, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The frequently occurring photoreceptor patterns in fish are explained using functional and environmental demands in a geometric model. The shape of the double cone provides a number of constructional properties leading to a limited number of appropriate configurations. The probability of their occurrence is estimated from the degree to which the combination of properties of each configuration meets specific environmental light conditions. A row pattern of merely double cones is especially suitable for vision in a dim homochromatic environment; a triangular (...) pattern is quite appropriate for high resolution and accurate movement detection, whereas the known square pattern has a high adaptive capacity to varying spectral distributions. In this context the transforming capacities of both square and row patterns can be understood. (shrink)

The candidate gene approach has identified many causes of photoreceptor rod cell death in retinitis pigmentosa. Some mutations lead to increased cyclicGMP concentrations in rods. Rod photoreceptors are also particularly susceptible to some mutations in housekeeping genes. Although many more cases of macular degeneration than retinitis pigmentosa occur each year, there is much less known about both genetic and sporadic forms of this disease.

The shape and turnover of photoreceptor membranes appears to depend on associated actin filaments. In dipterans, the photoreceptor membrane is microvillar. It is turned over by the addition of new membrane at the bases of the microvilli and by subsequent shedding, mostly from the distal ends. Each microvillus contains actin filaments as a component of its cytoskeletal core. Two myosin I‐like proteins co‐localize with the actin filaments. It is suggested that one of the myosin I‐like proteins might be linked to (...) the microvillar membrane. By interacting with the actin filaments, this motor should move the membrane of a microvillus in a distal direction, thus providing a possible mechanism for the turnover of the membrane.A vertebrate photoreceptor cell contains a small cluster of actin filaments in its connecting cilium at the site where new transductive disk membranes are formed. Disruption of the actin filaments perturbs disk morphogenesis. The most likely explanation for this perturbation is that the process of initiating a new disk is inhibited. Conventional myosin (myosin II) is found in the connecting cilium with the same distribution as actin. A simple model is proposed to illustrate how the actin–myosin system of the connecting cilium might function to initiate the morphogenesis of a disk membrane. (shrink)

The influence of light on the lives of living organisms is all-pervasive, affecting movement, vision, behavior, and physiological activity. This book is a biophysically grounded comparative survey of how animals detect light and perceive their surroundings. Included are discussions of photoreceptors, light emitters, and eyes. The book focuses in particular on the kinds of optical systems that have evolved, beginning with unicellular organisms that detect and respond to light through to more advanced and complex designs for imaging. The relevance (...) of these studies extends beyond biology, since these findings can be used to help develop photoreceptor energy conversion and information systems, and optical imaging devices with a wide range of everyday applications. The book will appeal to biophysicists, photobiologists, bioengineers, neuroscientists, and all researchers working in the area of vision and visual optics. (shrink)

The primary sequence of two subunits of the rod and one subunit of the cone cGMP-gated channel have been described, but describing how structure determines function is only just beginning. The discovery that the affinity of the rod channel for its agonist can be modulated indicates that the relationship between intracellular cGMP and the channel's open probability (current) during the course of the photoresponse may be more complex than previously thought.

The cyclic GMP-gated channel responds to changes in free intracellular cGMP, and as a result, it plays a central role in the phototransduction process in rod and cone photoreceptor cells. Recent biochemical, immunochemical, and molecular biology studies indicate that this channel consists of a complex of two distinct subunits and one or more associated proteins. Primary structural analysis indicates that the a and (3 subunits contain a cGMP-binding domain, an even number of membrane-spanning segments, a voltage sensor motif and a (...) pore region. The latter two features are found in voltage-gated channels and suggest that these two classes of channels have evolved from the same ancestral channel protein. A working model for the membrane topography of the channel subunits is proposed based on immunogold labeling studies and sequence analysis. Recent studies also indicate that calmodulin binds to the 240 kDa protein of the channel complex and modulates the sensitivity of the channel for cGMP in a Ca2+-dependent manner. The molecular properties of the channel complex and the possible role of Ca2+-calmodulin modulation of the channel during photoactivation and photorecovery are discussed in relation to the current mechanism of phototransduction in photoreceptor cells. (shrink)

The Drosophila compound eye is an excellent experimental system for analysing fate induction of identifiable single cells. Each ommatidium, a unit eye, contains eight photoreceptors (R1‐R8), and the differentiation of these photoreceptors occurs in the larval eye imaginal disc in discrete steps: first R8 is determined, then R2/R5, R3/R4, R1/R6 and finally R7. Induction of R7, in particular, has been extensively studied at the molecular level. The R8 photoreceptor presents on its surface a ligand, Bride of Sevenless, that (...) binds and activates Sevenless receptor tyrosine kinase in the R7 precursor. Autophosphorylated Sevenless initiates a Ras1‐mediated cascade, which eventually activates transcription factors in the nucleus via Raf1 and MAP kinases, resulting in R7 development. However, recent studies indicate that Sevenless (Sev) functions just to neuralize the cell and has no role in R7 fate determination per se. It appears that the R7 fate may represent the lowest rung of a ‘neuronal ground state’, which is attained without any specific inductive cue. It is plausible that the R7 precursor is actively prevented from taking on the neuronal fate and this inhibition is removed by activation of Sev. (shrink)

This article evaluates each of the reactions known to be involved in visual transduction as a potential site for the regulation of light adaptation. Extensive evidence suggests that calcium acts as a feedback messenger at several different points and recent work suggests a role for cGMP in regulating the primary excitatory pathway. A conclusion is that adaptation is likely to be regulated by multiple and redundant mechanisms. The goal of future experimentation will be to determine the relative importance of each (...) of these. (shrink)

Abnormalities in the ability of cells to properly degrade proteins have been identified in many neurodegenerative diseases. Recent work has implicated synaptojanin 1 (SynJ1) in Alzheimer's disease and Parkinson's disease, although the role of this polyphosphoinositide phosphatase in protein degradation has not been thoroughly described. Here, we dissected in vivo the role of SynJ1 in endolysosomal trafficking in zebrafish cone photoreceptors using a SynJ1‐deficient zebrafish mutant, nrca14. We found that loss of SynJ1 leads to specific accumulation of late endosomes (...) and autophagosomes early in photoreceptor development. An analysis of autophagic flux revealed that autophagosomes accumulate because of a defect in maturation. In addition we found an increase in vesicles that are highly enriched for PI(3)P, but negative for an early endosome marker in nrca14 cones. A mutational analysis of SynJ1 enzymatic domains found that activity of the 5'phosphatase, but not the Sac1 domain, is required to rescue both aberrant late endosomes and autophagosomes. Finally, modulating activity of the PI(4,5)P2 regulator, Arf6, rescued the disrupted trafficking pathways in nrca14 cones. Our study describes a specific role for SynJ1 in autophagosomal and endosomal trafficking and provides evidence that PI(4,5)P2 participates in autophagy in a neuronal cell type. -/- . (shrink)

Analysis of the light‐induced changes of cytosolic Ca2+ ([Ca2+]i) in photoreceptor cells has been taken a step further with two recently published studies(1,2). In one, changes in [Ca2+]i were measured in single detached rod outer segments from Gecko in response to various light intensities. The advances of the other(2) are embodied in its employment of transgenic Drosophila, whose photoreceptors express a visual pigment that is insensitive to the wavelength of light used in the fluorescence imaging of [Ca2+]i. These studies (...) provide a better basis for understanding the regulation of Ca2+‐mediated events in photoreceptor cells. (shrink)

Recoverin is a Ca2+-binding protein found primarily in vertebrate photoreceptors. The proposed physiological function of recoverin is based on the finding that recoverin inhibits light-stimulated phosphorylation of rhodopsin. Recoverin interacts with rod outer segment membranes in a Ca2+-dependent manner. This interaction requires N-terminal acylation of recoverin. Four types of fatty acids have been detected on the N-terminus of recoverin, but the functional significance of this heterogeneous acylation is not yet clear.

Light adaptation is modulated almost exclusively by changes in intracellular Ca2+ concentration, and other Ca2+-independent mechanisms are likely to play only a minor role. Changes in Ca2+i may be not only necessary for light adaptation to take place but sufficient to cause it.

Cyclic nucleotides can regulate the sensitivity of retinal rods to light through phosducin. The phosphorylation state of phosducin determines the amount of G available for activation by Rho*. Phosducin phosphorylation is regulated by cyclic nucleotides through their activation of cAMP-dependent protein kinase. The regulation of phosphodiesterase activity by the noncatalytic cGMP binding sites as well as Ca2+/calmodulin dependent regulation of cGMP binding to the cation channel are also discussed.

Rod photoreceptors are among the most sensitive light detectors in nature. They achieve their remarkable sensitivity across a wide variety of species through a number of essential adaptations: a specialized cellular geometry, a G‐protein cascade with an unusually stable receptor molecule, a low‐noise transduction mechanism, a nearly perfect effector enzyme, and highly evolved mechanisms of feedback control and receptor deactivation. Practically any change in protein expression, enzyme activity, or feedback control can be shown to impair photon detection, either by (...) decreasing sensitivity or signal‐to‐noise ratio, or by reducing temporal resolution. Comparison of mammals to amphibians suggests that rod outer‐segment morphology and the molecules and mechanism of transduction may have evolved together to optimize light sensitivity in darkness, which culminates in the extraordinary ability of these cells to respond to single photons at the ultimate limit of visual perception. (shrink)

To understand how the photoreceptor protein rhodopsin performs in its role as a receptor, its structure needs to be determined at the atomic level. Upon receiving a photon of light, rhodopsin undergoes a change in conformation that allows it to bind and activate the C-protein, transducin. An important future goal should be to determine the structure of both the inactive and the photoactivated state of rhodopsin, R*. This should provide the groundwork necessary for experiments on how rhodopsin achieves its signaling (...) state R*, and how R* functions to activate transducin. To do this, the crystal structure of both rhodopsin and R* must be determined. Few membrane proteins have been successfully crystallized, so this is not a trivial undertaking. Two- or three dimensional crystals of rhodopsin must be prepared that are well ordered, to produce a high-resolution structure. Rhodopsin must be purified to homogeneity and the appropriate detergent(s) selected for crystallization experiments. Long-term thermal stability of the rhodopsin-detergent complex must be achieved in the presence of a precipitant. Two-dimensional crystals may offer advantages in investigating the structure of R*, but the structure obtained may be limited in resolution. It is necessary to work with rhodopsin in the dark, unless suitable light-stable retinal derivatives are developed. Protein engineering of rhodopsin offers attractive opportunities to improve its ability to crystallize, but is presently hindered by the absence of a high-yielding expression system. Knowledge of the structure of rhodopsin will have general importance. Because rhodopsin is a member of the family of C-protein-coupled receptors, knowledge of the structure and the mechanism of action of rhodopsin suggests by analogy how other members of the receptor family may function. (shrink)

The vertebrate retina is said to be inverted because the photoreceptors are oriented in the posterior direction and are thus unable to maximize photodetection under conditions of low illumination. The tapetum lucidum is a photoreflective structure located posterior to the photoreceptors in the eyes of some fish and terrestrial animals. The tapetum reflects light forward, giving incident photons a “second chance” to collide with a photoreceptor, substantially enhancing retinal photosensitivity in dim light. Across vertebrates (and arthropods), there are (...) a wide variety of tapeta that vary in structure, chemical composition, and even tissue architecture, indicating repeated convergent evolution. To date, the tapetum has not been observed in any cephalopod, however, which also possess a camera‐like eye, but with the retinal photoreceptors oriented in the anterior direction. We therefore hypothesize that the tapetum lucidum is a compensatory adaptation for the suboptimal design of the inverted retina of vertebrates. (shrink)

Vertebrates respond to light with more than just their eyes. In this article, we speculate on the intriguing possibility that a link remains between non‐visual opsins and neurohormonal systems that control neuronal circuit formation and activity in mammals. Historically, the retina and pineal gland were considered the only significant light‐sensing tissues in vertebrates. However over the last century, evidence has accumulated arguing that extra‐ocular tissues in vertebrates influence behavior through non‐image‐forming photoreception. One such class of extra‐ocular light detectors are the (...) long mysterious deep brain photoreceptors. Here, we review recent findings on the cellular identity and the function of deep brain photoreceptors controlling behavior and physiology in zebrafish, and discuss their implications. (shrink)

Diseases causing inherited retinal degeneration in humans, such as retinitis pigmentosa and macular dystrophy, are genetically heterogeneous and clinically diverse. More than 40 genes causing retinal degeneration have been mapped to specific chromosomal sites; of these, at least 10 have been cloned and characterized. Mutations in two proteins, rhodopsin and peripherin/RDS, account for approximately 35% of all cases of autosomal dominant retinitis pigmentosa and a lesser fraction of other retinal conditions. This target article reviews the genes and mutations causing retinal (...) degeneration and proposes mechanisms whereby specific mutations lead to particular clinical consequences, that is, the relationship between genotype and phenotype. Retinitis pigmentosa and macular dystrophy are genetically heterogeneous diseases that cause retinal degeneration in humans and often result in severe visual impairment or blindness. Although many of the genes causing these diseases have not been identified, three photoreceptor-specific proteins have been implicated: rhodopsin, peripherin/RDS, and the P-subunit of rod phosphodiesterase. Mutations in the genes for these three proteins can cause either dominant retinitis pigmentosa, recessive retinitis pigmentosa, dominant congenital stationary night blindness, or dominant macular degeneration. Why this multiplicity of clinical phenotypes? Our target article summarizes the genetic and biochemical background to this question and proposes a number of possible explanations. Discussion focuses mainly on 73 distinct disease-causing mutations of rhodopsin. We feel that rhodopsin and other photoreceptor proteins can serve as model systems for unraveling the connection between genotype and phenotype, not only for inherited retinal diseases but for other degenerative disorders as well. (shrink)

Vertebrates respond to light with more than just their eyes. In this article, we speculate on the intriguing possibility that a link remains between non‐visual opsins and neurohormonal systems that control neuronal circuit formation and activity in mammals. Historically, the retina and pineal gland were considered the only significant light‐sensing tissues in vertebrates. However over the last century, evidence has accumulated arguing that extra‐ocular tissues in vertebrates influence behavior through non‐image‐forming photoreception. One such class of extra‐ocular light detectors are the (...) long mysterious deep brain photoreceptors. Here, we review recent findings on the cellular identity and the function of deep brain photoreceptors controlling behavior and physiology in zebrafish, and discuss their implications. (shrink)

In photoreceptors of a dark adapted eye, the inward flux of sodium and calcium ions in the outer segment is balanced by the outward flux of potassium ions. But in the presence of light the creation of cyclic guanosine monophosphate in the outer segment decreases. Due to low concentration of cG the channels in the outer segment open relatively less and thus the influx of calcium ion decreases, leading finally to hyperpolarization of the photoreceptors. We have analyzed theoretically (...) the effect of oxidizing iron ions on the photoreceptors. In order to explain the effects of iron-induced oxidative stress, the different molecules and ions involved in phototransduction are quantified leading to a differential equation for calculating the electroretinogram a-wave voltage. The theoretical results are compared with published experimental data. In the presence of light, the iron ions could push outward the similarly charged calcium ions resulting in a small increase in the amount of inward calcium flux. Again, the presence of iron ions generates Reactive Oxygen Species, and ROS could attract the calcium ions which also increases the calcium flux. This will result in a reduction in the amplitude and slope of the a-wave voltage in the electroretinogram. These results are parametrized in terms of calcium ion concentrations. As the amplitude of the a-wave shows how much electrical signal is produced, its reduction indicates reduction in the visual signal. Thus, the increase in iron ions could explain the reduction in the electrical signal due to iron-induced oxidative stress. (shrink)

Visual experience is shaped by a number of factors that are independent of the external objects that we perceive—factors like lighting, angle of view, and the sensitivities of photoreceptors in the retina. This paper seeks to catalog, analyze, and explain the fluctuations in visual phenomenology that are due to such factors.

A range of arguments are presented to demonstrate that (1) human visual orientations are conceptually constituted (concept?bound); (2) the concept?boundedness of visual orientations does not require a cognitivist account according to which a mental process of ?inference? or of ?interpretation? must be postulated to accompany a purely ?optical? registration of ?wavelengths of light?, ?photons?, or contentless ?information'; (3) concept?bound visual orientations are not all instances of ?seeing as?, contrary to some currently prominent cognitivist accounts; (4) the dispute between cognitivist and (...) realist accounts about the phenomenon of ?seeing as? is spurious, and is based upon a confusion about the fundamental analytical distinction made by Wittgenstein between ?seeing? and ?seeing as'; (5) ?perceiving?, ?seeing?, and ?seeing as? are but three of a large array of verbs of human visual orientation, and are not ?master categories? under which one can subsume these other modalities; (6) one cannot deduce a continuity of human visual orientation from a continuity of photon?photoreceptor interaction, a point we characterize as the ?staggered character? of human visual orientations; (7) detailed attention to the grammars of the diverse verbs of human visual orientation can open up a domain of study which we here refer to as a ?praxiology of perception'; (8) the nature of such an inquiry can be illustrated with exemplary reference to the analysis of the properties of ?noticing? as embedded in courses of practical action; and (9) such arguments, which claim that existing perceptual theories overly homogenize what is involved in visual orientations to the world, parallel those of Stroll, who proposes that standard accounts of ?what is perceived? overly homogenize the perceptible environment. (shrink)

: According to a consensus of psycho-physiological and philosophical theories, color sensations (or qualia) are generated in a cerebral "space" fed from photon-photoreceptor interaction (producing "metamers") in the retina of the eye. The resulting "space" has three dimensions: hue (or chroma), saturation (or "purity"), and brightness (lightness, value or intensity) and (in some versions) is further structured by primitive or landmark "colors"—usually four, or six (when white and black are added to red, yellow, green and blue). It has also been (...) proposed that there are eleven semantic universals—labeling the previous six plus the "intermediaries" of orange, pink, brown, purple, and gray. There are many versions of this consensus, but they all aim to provide ontological, epistemological and semantic blueprints for the brute fact of the reality of color ordained by Nature (evolution). In contrast to this consensus, we have argued that "seeing color" is not a matter of light waves impacting on our eyes, producing sensations to be categorized and labeled in the "color space" in the brain. While electrochemical events may unproblematically be regarded as the causal precondition for seeing color, the reception of sensations in "the color space" as semantically labeled natural categories, kinds, or information, is a "just so" story: it is Wittgenstein's beetle in a box. In contrast we consider that the authority of this consensus might better be regarded not as the result of the truth-tracking of nature, but as the sociohistorical outcome of philosophical presuppositions, scientific theories, experimental practices, technological apparatus, and their feed forward into the lifeworld. The question we shall therefore explore is whether, or to what extent, we ourselves are changed, as the conditions of production of color science change. Thus we are doing a kind of anthropology at two levels: of color science itself (and its effect on our own lifeworld), and of those studied by the "anthropology of color". As befits this stance we are agnostic about the theoretical entities of color science (cf. van Fraassen 2001), and within this new context, we propose to cross-cut object-and-subject, organism-and-environment (the bedrock of color science) in socio-historical ways. Our approach is in part inspired by, but not the same as, that of Gibson, in that we wish to pursue the notion of "social affordances" (Burmudez 1995). We suggest that color has become a naturalization through science-based technologies, which, through praxes and materializations, have become the perceptual and cultural entities that structure experience and understanding in the lifeworld. It is this naturalization that we shall refer to and characterize as "the historically inflected exosomatic organ". Consequently we shall explore the historical ontology of "color" without assuming an underlying biological constant (Dupré 2001). In part 1 we show the flimsiness of the evidence for the three dimensions of color, borrowed from physics, and fine-tuned to a "standard observer" (a "spectral creature" with a phenomenal "color space"). In part 2 we address the structuring of hue through the development of color circles and color spaces. This is followed by a review of the evidence for unique hues. Again the evidence is shown to be flimsy. We then show that an isolated domain of color is a particular kind of model, not a "natural given". In part 3, after reviewing what is referred to as "the isomorphy thesis," we discuss the exemplary case study of Berlin and Kay (1969). This illustrates the pull of stadial models presupposed by their evolutionary theory of color language. The Berlin and Kay paradigm proposes that American English color terms are incorrigible and can provide the universal metalanguage. We conclude by presenting an alternative account, namely that we ourselves are changed as the conditions of production of color science change. We argue that it is better to regard "seeing-color" as a historically inflected exosomatic organ that provides social affordances for those trained to grasp them. (shrink)

It has been suggested that difficult-to-quantify differences in visual processing may prevent researchers from equating the color experience of different observers. However, spectral locations of unique hues are remarkably invariant with respect to everything other than gross differences in preretinal and photoreceptor absorptions. This suggests a stereotyping of neural color processing and leads us to posit that minor differences in observer neurophysiology may be irrelevant to color experience.

When we perceive the external world, our brain has to deal with the incompleteness and uncertainty associated with sensory inputs, memory and prior knowledge. In theoretical neuroscience probabilistic approaches have received a growing interest recently, as they account for the ability to reason with incomplete knowledge and to efficiently describe perceptive and behavioral tasks. How can the probability distributions that need to be estimated in these models be represented and processed in the brain, in particular at the single cell level? (...) We consider the basic function carried out by photoreceptor cells which consists in detecting the presence or absence of light. We give a system-level understanding of the process of phototransduction based on a bayesian formalism: we show that the process of phototransduction is equivalent to a temporal probabilistic inference in a Hidden Markov Model (HMM), for estimating the presence or absence of light. Thus, the biochemical mechanisms of phototransduction underlie the estimation of the current state probability distribution of the presence of light. A classical descriptive model describes the interactions between the different molecular messengers, ions, enzymes and channel proteins occurring within the photoreceptor by a set of nonlinear coupled differential equations. In contrast, the probabilistic HMM model is described by a discrete recurrence equation. It appears that the binary HMM has a general solution in the case of constant input. This allows a detailed analysis of the dynamics of the system. The biochemical system and the HMM behave similarly under steady-state conditions. Consequently a formal equivalence can be found between the biochemical system and the HMM. Numerical simulations further extend the results to the dynamic case and to noisy input. All in all, we have derived a probabilistic model equivalent to a classical descriptive model of phototransduction, which has the additional advantage of assigning a function to phototransduction. The example of phototransduction shows how simple biochemical interactions underlie simple probabilistic inferences. (shrink)

Molday and Hsu review results from in vitro experiments, which indicate that Ca-bound calmodulin reduces the cGMP sensitivity of the cyclic nucleotide-gated channel of photoreceptor cells, and speculate about the role they might play in the recovery of the light response. We discuss results from in vivo experiments that argue against the participation of Ca-calmodulin in photorecovery.

Exaptations are adaptations that have undergone a major change in function. By recruiting genes from sources originally unrelated to vision, exaptation has allowed for sudden and critical photosensory innovations, such as lenses, photopigments, and photoreceptors. Here we review new or neglected findings, with an emphasis on unicellular eukaryotes (protists), to illustrate how exaptation has shaped photoreception across the tree of life. Protist phylogeny attests to multiple origins of photoreception, as well as the extreme creativity of evolution. By appropriating genes (...) and even entire organelles from foreign organisms via lateral gene transfer and endosymbiosis, protists have cobbled photoreceptors and eyespots from a diverse set of ingredients. While refinement through natural selection is paramount, exaptation helps illustrate how novelties arise in the first place, and is now shedding light on the origins of photoreception itself. -/- . (shrink)

This chapter examines a question at the intersection of the mind-body problem and the analysis of mental representation: the question of the direction of constraint between psychological fact and theory and neurophysiological or physical fact and theory. Does physiology constrain psychology? Are physiological facts more basic than psychological facts? Or do psychological theories, including representational analyses, guide and constrain physiology? Despite the antireductionist bent of functionalist positions, it has generally been assumed that physics or physiology are more basic than, and (...) hence contraining on, psychological fact and theory. Section 1 sketches the intuitions that would lead one to adopt such a view. The chapter then examines whether one-sided constraint has been and should be found in practice. It argues that philosophical analysis of psychological science shows that rigorous functional analyses can be carried out in advance of physiological knowledge. Indeed, in the investigation of sensory perception, ascription of psychological function leads the way in the individuation and investigation of neurophysiology. We shall look at several cases in visual perception (binocular single vision, stereopsis, and color vision), in which psychological results have provided a basis for physiological research. It is tempting to think that the psychological functions that enable physiological investigation would be Wrightian teleofunctions. It is, thus, natural to suppose that psychologists and neurophysiologists have proceeded with a conception of the purpose of a given neural structure, and have viewed neural anatomy and neural activity as the substrate for or instantiation of various properly psychological functions. For example, neuroscientists surely understand that the eye and visual system are for seeing, rather than for detecting an electric discharge in the vicinity of the retina (which sighted humans can do, via the subjective light produced by such discharges), and they guide their investigations of the eye, visual cortex, and intervening pathways accordingly. As a result, they will view rods and cones in the eye as photoreceptors, even though these structures will produce "output" (will respond with hyperpolarization) to other forms of energy. At the same time, there may be cases in which the functions that have guided research are in fact precisely determined input-output functions, whose teleofunctional status is absent or misdescribed. I will argue that in the case of trichromatic color matches, the psychological function involved is an input-output function, and that this result has implications for the description of color vision as a psychological capacity. (shrink)

The physiological blind spot corresponds to the optic disc where the retina contains no light-detecting photoreceptor cells. Our perception seemingly fills in this gap in input. Here we suggest that rather than an active process, such perceptual filling-in could instead be a consequence of the integration of visual inputs at higher stages of processing discounting the local absence of retinal input. Using functional brain imaging, we resolved the retinotopic representation of the physiological blind spot in early human visual cortex and (...) measured responses while participants perceived filling-in. Responses in early visual areas simply reflected the absence of visual input. In contrast, higher extrastriate regions responded more to stimuli in the eye containing the blind spot than the fellow eye. However, this signature was independent of filling-in. We argue that these findings agree with philosophical accounts that posit that the concept of filling-in of absent retinal input is unnecessary. (shrink)

Recent studies from several different laboratories have provided further insight into structure-function relationships of cyclic nucleotide-gated channel and in particular the cCMPgated channel of rod photoreceptors. Site-directed mutagenesis and rod-olfactory chimeria constructs have defined important amino acids and peptide segments of the channel that are important in ion blockage, ligand specificity, and gating properties. Molecular cloning studies have indicated that cyclic nucleotide-gated channels consist of two subunits that are required to reproduce the properties of the native channels. Biochemical analysis (...) of the cGMP-gated channel of rodcells have indicated that the 240 kDa protein that co-purifies with the 63 kDa channel subunit contains both the previously cloned second subunit of the channel and a glutamic acid-rich protein. The regulatory properties of the cGMP-gated channel from rod cells has also been studied in more detail. Studies indicate that the beta subunit of the cGMP-gated channel of rod cells contains the binding site for calmodulin. Interaction of calmodulin with the channel alters the apparent affinity of the channel for cGMP in all in vitro systems that have been studied. The significance of these recent studies are discussed in relation to the commentaries on the target article. (shrink)

The human visual system allows a number of molar activities, among them straightforward seeing and reflective seeing. Both of these activities include, as product and part of them, a stream of first-order, visual perceptual consciousness of the ecological environment and of the perceiver himself or herself as inhabiting the environment and acting or moving within it. The two respective component streams of first-order consciousness both proceed at certain brain centers and, in Gibson's sense, they are resonatings to the stimulus energy (...) flux at the photoreceptors. But the two streams differ in that only the one that proceeds during reflective seeing involves inner consciousness of the component first-order, visual perceptual consciousness . In this sense, perceptual consciousness proceeds entirely nonconsciously during straightforward seeing. This is because inner consciousness is not a kind of response to first-order consciousness, but is an intrinsic dimension of the latter when it is proceeding consciously as opposed to nonconsciously. The content of first-order, visual perceptual consciousness during reflective seeing is importantly different from the content during straightforward seeing, notwithstanding their both being kinds of seeing in the literal, nonmetaphorical sense as characterized by Gibson's ecological approach to visual perception. (shrink)

It is common to account for our senses on the basis of our sensory organs. One way of glossing why Aristotle famously counted five senses—and why his count became common sense in the West and elsewhere—is because there are five rather obvious organs of sense. In more modern accounts, this organ criterion of the senses has transformed into a neurobiological criterion; that is to say, part of what it means to be a sense is to have an associated organ with (...) appropriate physiological properties. For example, part of the claim that humans have a sense of vision is that we have a non-vestigial organ (the eye) that has cells (photoreceptors) especially sensitive to the properties of electromagnetic radiation. However, the nature of this “organ criterion” is a point of some contention. Is it a sufficient criterion? Necessary? To be called “vision” need the organ mediating it give rise to “visual experiences”? This chapter will consider the neurobiological criterion as it was originally presented in Aristotle and later reconceptualized in 19th-century neurophysiologist Johannes Müller’s “Law of Specific Nerve Energies.” By understanding the role of neurobiology in these accounts, we will be able to explore the deficiencies of contemporary accounts that downplay neurobiology in differentiating the senses. We will consider one of these accounts in detail: Alva Noë’s recent arguments in favor of an enactive approach to perceptual psychology. (shrink)

Determination of cell fate in the developing eye of Drosophila depends on a precise sequence of cellular interactions which generate the stereotypic array of ommatidia. In the eye imaginal disc, an initially unpatterned epithelial sheath of cells, the first step in this process may be the specification of R8 photoreceptor cells at regular intervals. Genes such as Notch and scabrous, known to be involved in bristle development, alos participate in this process, suggesting that the specification of ommatidial founder cells and (...) the formation of sensory organs in the adult epidermis may involve a similar mechanism, that of lateral inhibition. The subsequent steps of ommatidial assembly, following R8 assignment, involve a different mechanism: Undetermined cells read their position based on the contacts they make with neighbors that have already begun to differentiate. The development of the R7 photoreceptor cell, one of the eight photoreceptor cells in the ommatidium, is best understood. An important role seems to be played by sevenless, a receptor tyrosine kinase on the surface of the R7 precursor. It transmits the positional information– most likely encoded by the boss protein on the neighboring R8 cell membrane – into the cell via its tyrosine kinase, which activates a signal transduction cascade. Constitutive activation of the sevenless kinase by overexpression of an N‐terminally truncated form results in the diversion of other ommatidial cells into the R7 pathway suggesting that activation of the sevenless signalling pathway is sufficient to specify R7 development. Genetic dissection of this pathway should therefore identify components of a signalling cascade activated by a tyrosine kinase. (shrink)

This is a commentary on Laurence Maloney’s chapter in Mausfeld R., and Heyer, D. (Eds.): Colour Perception: Mind and the Physical World. Oxford: Oxford University Press, 2003. I discuss two related proposals as to the nature of object color formulated by Maloney. On the first proposal colors are photoreceptor excitations; on the second, they are fundamental, universal reflectance characteristics of terrestrial surfaces. I argue that the second proposal is suitable for purposes of color objectivism, whereas the first one is not. (...) However, if we look at Maloney’s – and Brian Wandell’s – models of color vision and color constancy more thoroughly, not even the second version supports absolutist versions of color objectivism, according to which observer-independent reflectance properties determine, or are identical to, the phenomenal character of color experience. (shrink)

The human fovea is known for its distinctive pit‐like appearance, which results from the displacement of retinal layers superficial to the photoreceptors cells. The photoreceptors are found at high density within the foveal region but not the surrounding retina. Efforts to elucidate the mechanisms responsible for these unique features have ruled out cell death as an explanation for pit formation and changes in cell proliferation as the cause of increased photoreceptor density. These findings have led to speculation that (...) mechanical forces acting within and on the retina during development underly the formation of foveal architecture. Here we review eye morphogenesis and retinal remodeling in human embryonic development. Our meta‐analysis of the literature suggests that fovea formation is a protracted process involving dynamic changes in ocular shape that start early and continue throughout most of human embryonic development. From these observations, we propose a new model for fovea development. (shrink)

Hereditary retinal degeneration due to mutations in visual genes may be amenable to therapeutic interventions that modulate, either positively or negatively, the amount of protein product. Some of the proteins involved in phototransduction are rapidly moved by a lightdependent mechanism between the inner segment and the outer segment in rod photoreceptor cells, and this phenomenon is important in phototransduction.

This review is focused on recent advances in our understanding of the development of coordinated cell polarity, through experiments on the Drosophila compound eye. Each eye facet (or “ommatidium”) contains a set of eight photoreceptor cells, placed so that their rhabdomeres form an asymmetric trapezoid. The array of ommatidia is organized so that these trapezoids are aligned in two mirror-image fields, dorsal and ventral to the eye midline (or “equator”). The development of this pattern depends on two systems of positional (...) information that inform the cluster of cells that will form an ommatidium of anterior/posterior (a/p) and dorsal/ventral (d/v) direction. The former (a/p) is encoded by a progressive wave of development (the morphogenetic furrow). The latter (d/v) involves molecules known to act in tissue polarity in other organs and organisms. Our understanding of the function of these molecules rests not only on their mutant phenotypes, biochemistry, and expression patterns, but also on the spatial effects when mutant patches of cells are made (genetic mosaics). BioEssays 21:275–285, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

In human languages, a palindrome reads the same forward as backward (e.g., ‘madam’). In regulatory DNA, a palindrome is an inverted sequence repeat that allows a transcription factor to bind as a homodimer or as a heterodimer with another type of transcription factor. Regulatory palindromes are typically imperfect, that is, the repeated sequences differ in at least one base pair, but the functional significance of this asymmetry remains poorly understood. Here, we review the use of imperfect palindromes in Drosophila photoreceptor (...) differentiation and mammalian steroid receptor signaling. Moreover, we discuss mechanistic explanations for the predominance of imperfect palindromes over perfect palindromes in these two gene regulatory contexts. Lastly, we propose to elucidate whether specific imperfectly palindromic variants have specific regulatory functions in steroid receptor signaling and whether such variants can help predict transcriptional outcomes as well as the response of individual patients to drug treatments. (shrink)

It may be possible, one day, to use gene therapy to treat diseases whose genetic defects have been discerned. Because many genes responsible for inherited eye disorders within the retina have been identified, diseases of the eye are prime candidates for this form of therapy. The eye also has the advantage of being highly accessible with altered immunological properties, important considerations for easy delivery of virus and avoidance of systemic immune responses. Currently, adenovirus, adeno‐associated virus and lentivirus have been used (...) to successfully transfer genetic material to retinal pigment epithelium and photoreceptor cells. By harnessing therapeutic genes to these viruses, researchers have been able to demonstrate rescue in rodent models of retinitis pigmentosa, providing evidence that this form of therapy can be effective in delaying photoreceptor cell death. Future challenges include confirming therapeutic effects in animal models with eyes more anatomically similar to those of humans and demonstrating long‐term rescue with minimal toxicity. BioEssays 23:662–668, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The striking color patterns of butterflies and birds have long interested biologists. But how these animals see color is less well understood. Opsins are the protein components of the visual pigments of the eye. Color vision has evolved in butterflies through opsin gene duplications, through positive selection at individual opsin loci, and by the use of filtering pigments. By contrast, birds have retained the same opsin complement present in early-jawed vertebrates, and their visual system has diversified primarily through tuning of (...) the short-wavelength-sensitive photoreceptors, rather than by opsin duplication or the use of filtering elements. Butterflies and birds have evolved photoreceptors that might use some of the same amino acid sites for generating similar spectral phenotypes across 540 million years of evolution, when rhabdomeric and ciliary-type opsins radiated during the early Cambrian period. Considering the similarities between the two taxa, it is surprising that the eyes of birds are not more diverse. Additional taxonomic sampling of birds may help clarify this mystery. (shrink)

The Drosophila Bolwig organs are small photoreceptor bundles that facilitate the phototactic behavior of the larva. Comparative literature suggests that these highly reduced visual organs share evolutionary ancestry with the adult compound eye. A recent molecular genetic study produced the first detailed account of the mechanisms controlling differential opsin expression and photoreceptor subtype determination in these enigmatic eyes of the Drosophila larva. Here, the evolutionary implications are examined, taking into account the dynamic diversification of opsin genes and the spatial regulation (...) of opsin homolog expression in other insects. It is concluded that, consistent with their common evolutionary roots, the Drosophila larval and adult eyes use the same mechanisms for the regulation of opsin expression and photoreceptor cell fate specification. Strikingly, the structurally highly derived Bolwig organs retained a more ancestral state of opsin expression and regulation. Inconspicuous in size, the Drosophila larval eyes deliver useful lessons in the reconstruction of homology between neuronal cell types with gene expression data, and on the conservative nature of gene regulatory network evolution during the emergence of novel organs from ancestral templates. BioEssays 30:980–993, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Recoverin is a 23 kDa Ca2+binding protein that has been detected primarily in vertebrate photoreceptors. The role of recoverin in phototransduction has been investigated using a variety of biochemical methods. Initial reports suggesting that recoverin regulates photoreceptor guanylyl cyclase have not been confirmed. Instead, recoverin appears to determine the lifetime of lightstimulated phosphodiesterase activity, perhaps by regulating rhodopsin phosphorylation. Retinal recoverin is heterogeneously fatty acylated at its ammo-terminus. The amino-terminal fatty acid appears to be involved in the interaction of (...) recoverin with photoreceptor membranes. (shrink)

The biochemical mechanism by which the phytochrome family of plant sensory photoreceptors transmit perceived informational light signals downstream to transduction pathway components is undetermined. The recent sequencing of the entire genome of the cyanobacterium Synechocystis, however, has revealed a protein that has an NH2‐terminal domain with striking sequence similarity to the photosensory NH2‐terminal domain of the phytochromes, and a COOH‐terminal domain strongly related to the transmitter histidine kinase module of bacterial two‐component sensors. The Synechocystis protein is capable of autocatalytic (...) chromophore ligation and exhibits photoreversible light‐absorption changes analogous to the phytochromes, indicating its capacity to function as an informational photoreceptor. Together with earlier observations that the COOH‐terminal domains of the plant phytochromes also have sequence similarity to the histidine kinases, these data suggest that the cyanobacteria utilize photoregulated histidine kinases as a sensory system and that the plant phytochromes may be evolutionary descendants of these photoreceptors. (shrink)