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Vision Research Oct 2018
Topics: Color Vision; Humans; Psychophysics; Retinal Cone Photoreceptor Cells
PubMed: 30327094
DOI: 10.1016/j.visres.2018.09.001 -
Advances in Experimental Medicine and... 2019Retinal imaging has advanced to enable noninvasive in vivo visualization of macular photoreceptors with cellular resolution. Images of retinal structure are best... (Review)
Review
Retinal imaging has advanced to enable noninvasive in vivo visualization of macular photoreceptors with cellular resolution. Images of retinal structure are best interpreted in the context of visual function, but clinical measures of visual function lack resolution on the scale of individual cells. Combined with cross-sectional measures of retinal structure acquired with optical coherence tomography (OCT), macular photoreceptor function can be evaluated using visual acuity and fundus-guided microperimetry, but the resolution of these measures is limited to relatively large retinal areas. By incorporating adaptive optics correction of aberrations in light entering and exiting the pupil, individual photoreceptors can be visualized and stimulated to assess structure and function. Discrepancy between structural images and visual function can shed light on the origin of visible features and their relation to visual function. Dysflective cones, cones with abnormal waveguiding properties on confocal adaptive optics scanning laser ophthalmoscopy (AOSLO) images and measurable function, provide insight into the visual significance of features in retinal images and may facilitate identification of patients who could benefit from therapies.
Topics: Fundus Oculi; Humans; Ophthalmoscopy; Retina; Retinal Cone Photoreceptor Cells; Tomography, Optical Coherence
PubMed: 31884601
DOI: 10.1007/978-3-030-27378-1_22 -
Pflugers Archiv : European Journal of... Sep 2021In the vertebrate retina, signals generated by cones of different spectral preference and by highly sensitive rod photoreceptors interact at various levels to extract... (Review)
Review
In the vertebrate retina, signals generated by cones of different spectral preference and by highly sensitive rod photoreceptors interact at various levels to extract salient visual information. The first opportunity for such interaction is offered by electrical coupling of the photoreceptors themselves, which is mediated by gap junctions located at the contact points of specialised cellular processes: synaptic terminals, telodendria and radial fins. Here, we examine the evolutionary pressures for and against interphotoreceptor coupling, which are likely to have shaped how coupling is deployed in different species. The impact of coupling on signal to noise ratio, spatial acuity, contrast sensitivity, absolute and increment threshold, retinal signal flow and colour discrimination is discussed while emphasising available data from a variety of vertebrate models spanning from lampreys to primates. We highlight the many gaps in our knowledge, persisting discrepancies in the literature, as well as some major unanswered questions on the actual extent and physiological role of cone-cone, rod-cone and rod-rod communication. Lastly, we point toward limited but intriguing evidence suggestive of the ancestral form of coupling among ciliary photoreceptors.
Topics: Animals; Gap Junctions; Humans; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Synapses
PubMed: 33988778
DOI: 10.1007/s00424-021-02572-9 -
Biochimica Et Biophysica Acta May 2014Cone visual pigments are visual opsins that are present in vertebrate cone photoreceptor cells and act as photoreceptor molecules responsible for photopic vision. Like... (Review)
Review
Cone visual pigments are visual opsins that are present in vertebrate cone photoreceptor cells and act as photoreceptor molecules responsible for photopic vision. Like the rod visual pigment rhodopsin, which is responsible for scotopic vision, cone visual pigments contain the chromophore 11-cis-retinal, which undergoes cis-trans isomerization resulting in the induction of conformational changes of the protein moiety to form a G protein-activating state. There are multiple types of cone visual pigments with different absorption maxima, which are the molecular basis of color discrimination in animals. Cone visual pigments form a phylogenetic sister group with non-visual opsin groups such as pinopsin, VA opsin, parapinopsin and parietopsin groups. Cone visual pigments diverged into four groups with different absorption maxima, and the rhodopsin group diverged from one of the four groups of cone visual pigments. The photochemical behavior of cone visual pigments is similar to that of pinopsin but considerably different from those of other non-visual opsins. G protein activation efficiency of cone visual pigments is also comparable to that of pinopsin but higher than that of the other non-visual opsins. Recent measurements with sufficient time-resolution demonstrated that G protein activation efficiency of cone visual pigments is lower than that of rhodopsin, which is one of the molecular bases for the lower amplification of cones compared to rods. In this review, the uniqueness of cone visual pigments is shown by comparison of their molecular properties with those of non-visual opsins and rhodopsin. This article is part of a Special Issue entitled: Retinal Proteins - You can teach an old dog new tricks.
Topics: Animals; Color Vision; Evolution, Molecular; Humans; Models, Molecular; Molecular Conformation; Opsins; Phylogeny; Retinal Cone Photoreceptor Cells; Retinaldehyde; Rhodopsin
PubMed: 24021171
DOI: 10.1016/j.bbabio.2013.08.009 -
Experimental Eye Research Dec 2020Bilallelic variants in the USH2A gene can cause Usher syndrome type 2 and non-syndromic retinitis pigmentosa. In both disorders, the retinal phenotype involves... (Review)
Review
Bilallelic variants in the USH2A gene can cause Usher syndrome type 2 and non-syndromic retinitis pigmentosa. In both disorders, the retinal phenotype involves progressive rod photoreceptor loss resulting in nyctalopia and a constricted visual field, followed by subsequent cone degeneration, leading to the loss of central vision and severe visual impairment. The USH2A gene raises many challenges for researchers and clinicians due to a broad spectrum of mutations, a large gene size hampering gene therapy development and limited knowledge on its pathogenicity. Patients with Usher type 2 may benefit from hearing aids or cochlear implants to correct their hearing defects, but there are currently no approved treatments available for the USH2A-retinopathy. Several treatment strategies, including antisense oligonucleotides and translational readthrough inducing drugs, have shown therapeutic promise in preclinical studies. Further understanding of the pathogenesis and natural history of USH2A-related disorders is required to develop innovative treatments and design clinical trials based on reliable outcome measures. The present review will discuss the current knowledge about USH2A, the emerging therapeutics and existing challenges.
Topics: DNA; DNA Mutational Analysis; Disease Management; Electroretinography; Extracellular Matrix Proteins; Genotype; Humans; Mutation; Phenotype; Retinal Cone Photoreceptor Cells; Retinal Diseases
PubMed: 33121974
DOI: 10.1016/j.exer.2020.108330 -
Current Biology : CB Dec 2020Retinal rod and cone photoreceptors mediate vision in dim and bright light, respectively, by transducing absorbed photons into neural electrical signals. Their...
Retinal rod and cone photoreceptors mediate vision in dim and bright light, respectively, by transducing absorbed photons into neural electrical signals. Their phototransduction mechanisms are essentially identical. However, one difference is that, whereas a rod visual pigment remains stable in darkness, a cone pigment has some tendency to dissociate spontaneously into apo-opsin and retinal (the chromophore) without isomerization. This cone-pigment property is long known but has mostly been overlooked. Importantly, because apo-opsin has weak constitutive activity, it triggers transduction to produce electrical noise even in darkness. Currently, the precise dark apo-opsin contents across cone subtypes are mostly unknown, as are their dark activities. We report here a study of goldfish red (L), green (M), and blue (S) cones, finding with microspectrophotometry widely different apo-opsin percentages in darkness, being ∼30% in L cones, ∼3% in M cones, and negligible in S cones. L and M cones also had higher dark apo-opsin noise than holo-pigment thermal isomerization activity. As such, given the most likely low signal amplification at the pigment-to-transducin/phosphodiesterase phototransduction step, especially in L cones, apo-opsin noise may not be easily distinguishable from light responses and thus may affect cone vision near threshold.
Topics: Animals; Darkness; Goldfish; Light Signal Transduction; Models, Animal; Opsins; Patch-Clamp Techniques; Photic Stimulation; Retinal Cone Photoreceptor Cells; Single-Cell Analysis
PubMed: 33065015
DOI: 10.1016/j.cub.2020.09.062 -
Scientific Reports Feb 2021Ca1.4 L-type calcium channels are predominantly expressed in photoreceptor terminals playing a crucial role for synaptic transmission and, consequently, for vision....
Ca1.4 L-type calcium channels are predominantly expressed in photoreceptor terminals playing a crucial role for synaptic transmission and, consequently, for vision. Human mutations in the encoding gene are associated with congenital stationary night blindness type-2. Besides rod-driven scotopic vision also cone-driven photopic responses are severely affected in patients. The present study therefore examined functional and morphological changes in cones and cone-related pathways in mice carrying the Ca1.4 gain-of function mutation I756T (Ca1.4-IT) using multielectrode array, patch-clamp and immunohistochemical analyses. Ca1.4-IT ganglion cell responses to photopic stimuli were seen only in a small fraction of cells indicative of a major impairment in the cone pathway. Though cone photoreceptors underwent morphological rearrangements, they retained their ability to release glutamate. Our functional data suggested a postsynaptic cone bipolar cell defect, supported by the fact that the majority of cone bipolar cells showed sprouting, while horizontal cells maintained contacts with cones and cone-to-horizontal cell input was preserved. Furthermore a reduction of basal Ca influx by a calcium channel blocker was not sufficient to rescue synaptic transmission deficits caused by the Ca1.4-IT mutation. Long term treatments with low-dose Ca channel blockers might however be beneficial reducing Ca toxicity without major effects on ganglion cells responses.
Topics: Animals; Calcium Channels, L-Type; Cell Shape; Mice; Mice, Transgenic; Retina; Retinal Cone Photoreceptor Cells; Synapses; Synaptic Transmission; Visual Pathways
PubMed: 33526839
DOI: 10.1038/s41598-021-82210-7 -
Journal of Vision Jun 2020The human fovea lies at the center of the retina and supports high-acuity vision. In normal visual system development, the highest acuity is correlated with both a high...
The human fovea lies at the center of the retina and supports high-acuity vision. In normal visual system development, the highest acuity is correlated with both a high density of cone photoreceptors in the fovea and a magnified retinotopic representation of the fovea in the visual cortex. Both cone density and the cortical area dedicated to each degree of visual space-the latter describing cortical magnification (CM)-steadily decrease with increasing eccentricity from the fovea. In albinism, peak cone density at the fovea and visual acuity are decreased, but seem to be within normal limits in the periphery, thus providing a model to explore the correlation between retinal structure, cortical structure, and behavior. Here, we used adaptive optics scanning light ophthalmoscopy to assess retinal cone density and functional magnetic resonance imaging to measure CM in the primary visual cortex of normal controls and individuals with albinism. We find that retinotopic organization is more varied among individuals with albinism than previously appreciated. Additionally, CM outside the fovea is similar to that in controls, but also more variable. CM in albinism and controls exceeds that which might be predicted based on cone density alone, but is more accurately predicted by retinal ganglion cell density. This finding suggests that decreased foveal cone density in albinism may be partially counteracted by nonuniform connectivity between cones and their downstream signaling partners. Together, these results emphasize that central as well as retinal factors must be included to provide a complete picture of aberrant structure and function in albinism.
Topics: Adolescent; Adult; Albinism; Cell Count; Female; Humans; Magnetic Resonance Imaging; Male; Ophthalmoscopy; Optics and Photonics; Retina; Retinal Cone Photoreceptor Cells; Retinal Ganglion Cells; Visual Acuity; Visual Cortex; Young Adult
PubMed: 32543650
DOI: 10.1167/jov.20.6.10 -
Survey of Ophthalmology 2020Retinitis pigmentosa 1-like 1 (RP1L1) is a component of the photoreceptor cilium. Pathogenic variants in RP1L1 lead to photoreceptor disease, suggesting an important... (Review)
Review
Retinitis pigmentosa 1-like 1 (RP1L1) is a component of the photoreceptor cilium. Pathogenic variants in RP1L1 lead to photoreceptor disease, suggesting an important role for RP1L1 in photoreceptor biology, though its exact function is unknown. To date, RP1L1 variants have been associated with occult macular dystrophy (a cone degeneration) and retinitis pigmentosa (a rod disease). Here, we summarize reported RP1L1-associated photoreceptor conditions and disease-causing RP1L1 variants. We also discuss novel associations between RP1L1 and additional photoreceptor conditions-besides occult macular dystrophy and retinitis pigmentosa-and fit RP1L1 into the broader scope of photoreceptor disease. RP1L1 appears to have a complex relationship with other photoreceptor proteins and may modify disease phenotype. Ultimately, further exploration of the relationship between RP1L1, other cilium components, and their impact on photoreceptor health is needed.
Topics: DNA; DNA Mutational Analysis; Electroretinography; Eye Proteins; Humans; Mutation; Phenotype; Retinal Cone Photoreceptor Cells; Retinal Diseases
PubMed: 32360662
DOI: 10.1016/j.survophthal.2020.04.005 -
Pflugers Archiv : European Journal of... Sep 2021All vertebrates share a canonical retina with light-sensitive photoreceptors in the outer retina. These photoreceptors are of two kinds: rods and cones, adapted to low... (Review)
Review
All vertebrates share a canonical retina with light-sensitive photoreceptors in the outer retina. These photoreceptors are of two kinds: rods and cones, adapted to low and bright light conditions, respectively. They both show a peculiar morphology, with long outer segments, comprised of ordered stacks of disc-shaped membranes. These discs host numerous proteins, many of which contribute to the visual transduction cascade. This pathway converts the light stimulus into a biological signal, ultimately modulating synaptic transmission. Recently, the zebrafish (Danio rerio) has gained popularity for studying the function of vertebrate photoreceptors. In this review, we introduce this model system and its contribution to our understanding of photoreception with a focus on the cone visual transduction cascade.
Topics: Animals; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Synapses; Vision, Ocular; Zebrafish
PubMed: 33598728
DOI: 10.1007/s00424-021-02528-z