An Atlas of the fine structure of the retina in Primates including humans.

The ontogeny of the vertebrate retina has been a topic of interest to developmental biologists and human geneticists for many decades. Understanding the unfolding of the genetic program that transforms a field of progenitors cells into a functionally complex and multi‐layered sensory organ is a formidable challenge. Although classical genetic studies succeeded in identifying the key regulators of retina specification, understanding the architecture of their gene network and predicting their behavior are still a distant hope. The emergence of next‐generation sequencing (...) platforms revolutionized the field unlocking the access to genome‐wide datasets. Emerging techniques such as RNA‐seq, ChIP‐seq, ATAC‐seq, or single cell RNA‐seq are used to characterize eye developmental programs. These studies provide valuable information on the transcriptional and cis‐regulatory profiles of precursors and differentiated cells, outlining the trajectories that connect each intermediate state. Here, recent systems biology efforts are reviewed to understand the genetic programs shaping the vertebrate retina. (shrink)

Over 10 years ago, Pax‐6 was shown to play an evolutionarily conserved role in controlling eye formation from Drosophila to humans.1 Since then, the identification of an entire cascade of conserved eye determination genes has brought a new understanding to the developmental relationship between the insect compound eye and the vertebrate camera eye.2 Additional studies are now beginning to suggest that even late aspects of eye development, including cell type specification, also share common molecular machinery. In this commentary, I will (...) discuss some of these findings, with a particular focus on the recent study by Dyer et al.3 describing a novel role for the Prox1 transcription factor in specifying horizontal cells in the mouse retina. As Prospero, the Drosophila homolog of Prox1, also participates in retinal cell specification, these data provide a forum for asking new questions concerning pathways that may regulate retinogenesis across evolution. BioEssays 25:921–925, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

ArgumentThis article explores the entangled histories of three imaging techniques in early nineteenth-century British physical science, techniques in which a dynamic event (such as a sound vibration or an electric spark) was made to leave behind a fixed trace on a sensitive surface. Three categories of “sensitive surface” are examined in turn: first, a metal plate covered in fine dust; second, the retina of the human eye; and finally, a surface covered with a light-sensitive chemical emulsion (a photographic plate). For (...) physicists Michael Faraday and Charles Wheatstone, and photographic pioneer William Henry Fox Talbot, transient phenomena could be studied through careful observation and manipulation of the patterns wrought on these different surfaces, and through an understanding of how the imaging process unfolded through time. This exposes the often-ignored materiality and temporality of epistemic practices around nineteenth-century scientific images said to be “drawn by nature.”. (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)

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)

The processing of information within the retino-tectal visual system of amphibians is decomposed into five major operational stages, three of them taking place in the retina and two in the optic tectum. The stages in the retina involve a spatially local high-pass filtering in connection to the perception of moving objects, separation of the receptor activity into ON- and OFF-channels regarding the distinction of objects on both light and dark backgrounds, spatial integration via near excitation and far-reaching inhibition. Variation of (...) the spatial range of excitation and inhibition allows to account for typical activities observed in a variety of classes of retina ganglion cells.Mathematical description of the operations in the tectum opticum include spatial summation of retinal output , and direct or indirect lateral inhibition between tectal cells. In the computer simulation, first the output of the mathematical retina model is computed which, then, is used as the input to the tectum model. The full spatio-temporal dynamics is taken into account.The simulations show that different combinations of strength of lateral inhibition on the one side and the response properties of the retina ganglion cells on the other side determine the response properties of tectal cell types involved in object recognition. (shrink)

The processing of information within the retino-tectal visual system of amphibians is decomposed into five major operational stages, three of them taking place in the retina and two in the optic tectum. The stages in the retina involve a spatially local high-pass filtering in connection to the perception of moving objects, separation of the receptor activity into ON- and OFF-channels regarding the distinction of objects on both light and dark backgrounds, spatial integration via near excitation and far-reaching inhibition. Variation of (...) the spatial range of excitation and inhibition allows to account for typical activities observed in a variety of classes of retina ganglion cells.Mathematical description of the operations in the tectum opticum include spatial summation of retinal output, and direct or indirect lateral inhibition between tectal cells. In the computer simulation, first the output of the mathematical retina model is computed which, then, is used as the input to the tectum model. The full spatio-temporal dynamics is taken into account.The simulations show that different combinations of strength of lateral inhibition on the one side and the response properties of the retina ganglion cells on the other side determine the response properties of tectal cell types involved in object recognition. (shrink)

Carotenoids play pivotal roles in vision as light filters and precursor of chromophore. Many vertebrates also display the colorful pigments as ornaments in bare skin parts and feathers. Proteins involved in the transport and metabolism of these lipids have been identified including class B scavenger receptors and carotenoid cleavage dioxygenases. Recent research implicates members of the Aster protein family, also known as GRAM domain‐containing (GRAMD), in carotenoid metabolism. These multi‐domain proteins facilitate the intracellular movement of carotenoids from their site of (...) cellular uptake by scavenger receptors to the site of their metabolic processing by carotenoid cleavage dioxygenases. We provide a model how the coordinated interplay of these proteins and their differential expression establishes carotenoid distribution patterns and function in tissues, with particular emphasis on the human retina. (shrink)

The processing of information within the retino-tectal visual system of amphibians is decomposed into five major operational stages, three of them taking place in the retina and two in the optic tectum. The stages in the retina involve (i) a spatially local high-pass filtering in connection to the perception of moving objects, (ii) separation of the receptor activity into ON- and OFF-channels regarding the distinction of objects on both light and dark backgrounds, (iii) spatial integration via near excitation and far-reaching (...) inhibition. Variation of the spatial range of excitation and inhibition allows to account for typical activities observed in a variety of classes of retina ganglion cells.Mathematical description of the operations in the tectum opticum include (i) spatial summation of retinal output (mainly of class-2 and class-3 retina ganglion cells), and (ii) direct or indirect lateral inhibition between tectal cells. In the computer simulation, first the output of the mathematical retina model is computed which, then, is used as the input to the tectum model. The full spatio-temporal dynamics is taken into account. (shrink)

In sensory biology, a major outstanding question is how sensory receptor cells minimize noise while maximizing signal to set the detection threshold. This optimization could be problematic because the origin of both the signals and the limiting noise in most sensory systems is believed to lie in stimulus transduction. Signal processing in receptor cells can improve the signal‐to‐noise ratio. However, neural circuits can further optimize the detection threshold by pooling signals from sensory receptor cells and processing them using a combination (...) of linear and nonlinear filtering mechanisms. In the visual system, noise limiting light detection has been assumed to arise from stimulus transduction in rod photoreceptors. In this context, the evolutionary optimization of the signal‐to‐noise ratio in the retina has proven critical in allowing visual sensitivity to approach the limits set by the quantal nature of light. Here, we discuss how noise in the mammalian retina is mitigated to allow for highly sensitive night vision. (shrink)

The ArgumentThis paper is concerned with the diversity of microscopic research in nineteenth-century life sciences. It examines how two researchers, Ernst Wilhelm Brücke and Heinrich Müller, investigated the structure and function of the retina. They did so in significantly different ways, thereby developing quite different accounts of this organ and its role in the process of vision. Both investigators were carrying out microscopic investigations, both were particularly concerned with interpreting their findings in terms of physiological function, and both employed the (...) physical sciences in their microscopic research. Their approaches differed, however, with respect to the manner of handling and preparing the tissues, as well as with respect to the conceptual tools they applied to their findings.The cases indicate that the common tendency to associate microscopic research mainly with morphological studies of organic material is not appropriate. To understand nineteenth-century microscopy and its place in the sciences of life, close attention should be paid to the manner in which microscopic investigations were performed. It is only then that the flexibility and versatility of microscopic research comes into view. (shrink)

The retina pigment epithelium (RPE) is a highly specialised epithelium that serves as a multifunctional and indispensable component of the vertebrate eye. Although a great deal of attention has been paid to its transdifferentiation capabilities and its ancillary functions in neural retina development, little is known about the molecular mechanisms that specify the RPE itself. Recent advances in our understanding of the genetic network that controls the progressive specification of the eye anlage in vertebrates have provided some of the initial (...) cues to the mechanisms responsible for RPE patterning. Here, we have outlined many recent findings that suggest that a limited number of transcription factors, including Otx2, Mitf and Pax6 and a few signalling cascades, are the elements required for the onset of RPE specification in vertebrates. Furthermore, using this information and the data available on the specification of the pigmented cells of primitive chordates, we have ventured some hypotheses on the origin of RPE cells during evolution. BioEssays 26:766–777, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Gene replacement therapy holds great promise in the treatment of many genetic CNS disorders. This commentary discusses the feasibility of gene replacement therapy in the unique context of the retina, with regard to: (1) the genetics of retinal neoplasia and degeneration, (2) available gene transfer technology, and (3) potential gene delivery vehicles.

Daily rhythms are a ubiquitous feature of living systems. Generally, these rhythms are not just passive consequences of cyclic fluctuations in the environment, but instead originate within the organism. In mammals, including humans, the master pacemaker controlling 24‐hour rhythms is localized in the suprachiasmatic nuclei of the hypothalamus. This circadian clock is responsible for the temporal organization of a wide variety of functions, ranging from sleep and food intake, to physiological measures such as body temperature, heart rate and hormone release. (...) The retinal circadian clock was the first extra‐SCN circadian oscillator to be discovered in mammals and several studies have now demonstrated that many of the physiological, cellular and molecular rhythms that are present within the retina are under the control of a retinal circadian clock, or more likely a network of hierarchically organized circadian clocks that are present within this tissue. BioEssays 30:624–633, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Colour constancy refers to the ability to extract information about surface colours independently of illumination conditions. A ripe strawberry, for example, appears the same red when viewed under a blue sky or a reddish sunset. Since Land's pioneering work, discussion has centred on the issue whether colour constancy is achieved primarily in the retina or visual cortex. Recently, the debate has shifted to a consideration of the constraints imposed by various psychophysical tasks and instructions. Humans can judge illuminant colour, reflected-light (...) colour, surface colour, and the relationship between surface colours within a scene. Such observations suggest that colour constancy may not be a unitary phenomenon, and that its different aspects may be mediated at different levels in the visual system. Several questions therefore arise: are the tasks of surface estimation and illuminant estimation complementary, insofar as good performance in one implies poor performance in the other? How does retinal adaptation alter performance? Is colour vision tuned to the statistical composition of natural surfaces and illuminants? What role does colour-opponent processing in retina and cortex play in colour constancy? These and related questions are explored here in order to better understand what we mean when we ask: "Why do strawberries look red?". (shrink)

Early and accurate diagnosis of glaucoma is critical for avoiding human vision deterioration and preventing blindness. A deep-neural-network model has been developed for the diagnosis of glaucoma based on Heidelberg retina tomography, called “Seeking Common Features and Reserving Differences Net” to make full use of the HRT data. In this work, the proposed SCRD-Net model achieved an area under the curve of 94.0%. For the two HRT image modalities, the model sensitivities were 91.2% and 78.3% at specificities of 0.85 and (...) 0.95, respectively. These results demonstrate a significant improvement over earlier results. In addition, we visualized the network outputs to develop an interpretation of the learned mechanism for discriminating glaucoma and normal images. Thus, the SCRD-Net can be an effective diagnostic indicator of glaucoma during clinical screening. To facilitate SCRD-Net utilization by the scientific community, the code implementation will be made publicly available. (shrink)

The complex sensation of vision begins with the relatively simple photoisomerization of the visual pigment chromophore 11-cis-retinal to its all-trans configuration. This event initiates a series of biochemical reactions that are collectively referred to as phototransduction, which ultimately lead to a change in the electrochemical signaling of the photoreceptor cell. To operate in a wide range of light intensities, however, the phototransduction pathway must allow for adjustments to background light. These take place through physiological adaptation processes that rely primarily on (...) Ca2+ ions. While Ca2+ may modulate some activities directly, it is more often the case that Ca2+-binding proteins mediate between transient changes in the concentration of Ca2+ and the adaptation processes that are associated with phototransduction. Recently, combined genetic, physiological, and biochemical analyses have yielded new insights about the properties and functions of many phototransduction-specific components, including some novel Ca2+-binding proteins. Understanding these Ca2+-binding proteins will provide a more complete picture of visual transduction, including the mechanisms associated with adaptation, and of related degenerative diseases. BioEssays 22:337–350, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Which roles are played by subcortical pathways in models of cortical streams for visual processing? Through their thalamic relays, magnocellular (M) and parvocellular (P) projecting ganglion cells send complementary signals to V1, where their outputs are combined in several different ways. The synergic role of M and P cells in vision can be understood by estimating cell response entropy in all domains of interest.

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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 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)