Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency

Baraas, Rigmor C.; Carroll, Joseph; Gunther, Karen L.; Chung, Mina; Williams, David R.; Foster, David H.; Neitz, Mary Jo

doi:10.1364/josaa.24.001438

Cited by 111 publications

(109 citation statements)

References 48 publications

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“…The position of cone photoreceptors were identified using a modified version of described automated Matlab software (32). Cone density was calculated using previously described methods relying on counting of the cones and spatial frequency analysis (24), and mosaic regularity and packing geometry was assessed using a previously described Voronoi analysis (50).…”

Section: Methodsmentioning

confidence: 99%

Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin

Carroll

Baraas

Wagner-Schuman

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Missense mutations in the cone opsins have been identified as a relatively common cause of red/green color vision defects, with the most frequent mutation being the substitution of arginine for cysteine at position 203 (C203R). When the corresponding cysteine is mutated in rhodopsin, it disrupts proper folding of the pigment, causing severe, early onset retinitis pigmentosa. While the C203R mutation has been associated with loss of cone function in color vision deficiency, it is not known what happens to cones expressing this mutant opsin. Here, we used high-resolution retinal imaging to examine the cone mosaic in two individuals with genes encoding a middle-wavelength sensitive (M) pigment with the C203R mutation. We found a significant reduction in cone density compared to normal and color-deficient controls, accompanying disruption in the cone mosaic in both individuals, and thinning of the outer nuclear layer. The C203R mosaics were different from that produced by another mutation (LIAVA) previously shown to disrupt the cone mosaic. Comparison of these mosaics provides insight into the timing and degree of cone disruption and has implications for the prospects for restoration of vision loss associated with various cone opsin mutations.color vision ͉ cone mosaic ͉ photopigment ͉ retinal imaging ͉ rhodopsin N ormal human color vision is trichromatic and derives from the presence of three spectrally distinct cone types: long-, middle-, and short-wavelength-sensitive (L, M, and S). Redgreen color vision defects are characterized by the absence of either L or M cone function and they affect about one in 12 Caucasian males. Inherited red-green defects can be linked to disruptions at the X-chromosome opsin gene locus, where the Land M-cone opsin genes reside in a head-to-tail array (1). Most of these disruptions involve gross gene rearrangements (2-6). However, it is becoming appreciated that missense mutations underlie a significant proportion of red-green defects (5-8). This raises the question of what impact these missense mutations have on the viability of the cones.Some insight comes from rhodopsin. There are Ͼ130 distinct rhodopsin mutations, involving at least 89 sites within the molecule (data compiled from refs. 9-17.) With rare exception (e.g., refs. 9 and 18), each of these mutations has been associated with either retinitis pigmentosa (RP) or congenital stationary night blindness. Rhodopsin and the cone opsins have structural similarities and similar functional demands. Thus, it is reasonable to hypothesize that mutations in the cone opsins homologous to those in rhodopsin that cause retinitis pigmentosa would affect the viability of the cones.The most common missense mutation in the cone opsins is a substitution of cytosine for thymine at nucleotide position 1101, which corresponds to a substitution of arginine for cysteine at amino acid position 203 (C203R) (Fig. S1). The corresponding mutation in rhodopsin (C187Y) disrupts proper folding of the pigment, causing severe, early onset retinitis pigmentos...

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Section: Methodsmentioning

confidence: 99%

Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin

Carroll

Baraas

Wagner-Schuman

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…However, sophisticated optical imaging suggests that some forms of dichromacy may occur through a 'loss' mechanism, resulting from the loss of a cone class with a concomitant reduction in the cone population. 8,9 Although the majority of dichromats are thought to enjoy otherwise normal visual function, there is some suggestion that a minority (with a presumed 'loss' mechanism) may perhaps have reduced visual function (see below). 10 …”

Section: Dichromacymentioning

confidence: 99%

“…9 As the blue cones represent only approximately 7% of the total cone population, the effects on visual function of blue cone photopigment mutations appear to be limited to colour vision deficiency.…”

Section: Is Congenital Colour Vision Deficiency a Form Of Retinal Dysmentioning

confidence: 99%

Colour vision deficiency

Simunovic

2009

Eye

161

148

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“…Tam et al, 2010 has improved the imaging of retinal vasculature without the need for fluorescein by using motion contrast to identify vessels, setting the stage for automated measurements of leukocyte velocity (Tam et al, in press). In vivo studies of blood flow in these smallest of vessels may provide valuable information about early vascular changes in diseases such as diabetic retinopathy.The clinical utility of AO imaging is only now beginning to be explored (Baraas et al, 2007;Bhatt et al, 2010;Carroll et al, 2004Carroll et al, , 2009Carroll et al, , 2010Choi et al, 2006;Chen et al, 2010;Hammer et al, 2008;McAllister et al, 2010;Talcott et al, 2010;Wolfing et al, 2006;Yoon et al, 2009). An exciting recent paper has also shown the potential of AO in drug development (Talcott et al, 2011).…”

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Imaging Single Cells in the Living Retina

Williams

2012

Frontiers in Optics 2012/Laser Science XXVIII

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A quarter century ago, we were limited to a macroscopic view of the retina inside the living eye. Since then, new imaging technologies, including confocal scanning laser ophthalmoscopy, optical coherence tomography, and adaptive optics fundus imaging, transformed the eye into a microscope in which individual cells can now be resolved noninvasively. These technologies have enabled a wide range of studies of the retina that were previously impossible. Keywordsretinal imaging; confocal scanning laser ophthalmoscope; adaptive optics; optical coherence tomography; spatial resolution; ophthalmoscopy The ability to look inside the living human eye is central to our understanding of how the normal eye works and the diseased eye fails. This article focuses on technological advances in the spatial resolution of retinal imaging during the last quarter century and some of the scientific discoveries they have made possible. These advances have transformed retinal imaging from a macroscopic to a microscopic modality in which individual cells can now be resolved. There are many books and review articles that address these advances. Relevant books include Masters, 2001;Porter et al, 2006; Schulman et al., 2004) and review articles include (Costa, et al., 2006;Drexler and Fujimoto, 2008;Fujimoto, 2003;Godara et al., 2010;Hampson, 2008;Miller et al., 2011;Miller and Roorda, 2009; Mojtkowski, 2010;Podoleanu, 2005;Podoleanu and Rosen, 2008;Roorda, 2010; Rossi et al. 2011;and Wilt et al., 2009).It has never been easy to peer inside the living eye. Though several investigators in the 19 th century were aware of the illumination conditions necessary to cause the otherwise impenetrable pupil to glow red, they failed to obtain a clear view of the living retina until Helmholtz invented the ophthalmoscope (Helmholtz, 1851). Since then, the evolution of this instrument has been punctuated by important, if occasional, technical advances such as adding a camera that could record retinal images on film (Jackman and Webster, 1886).© 2011 Elsevier Ltd. All rights reserved.Corresponding Author: David Williams. Conflict of Interest Disclosure: My employer, the University of Rochester, holds intellectual property on which I am an inventor and that pertain to the subject matter of this article.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptVision Res. Author manuscript; available in PMC 2012 July 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptSurprisingly, before the late 1980's there were few improvements in optical resolution sin...

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Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency

Cited by 111 publications

References 48 publications

Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin

Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin

Colour vision deficiency

Imaging Single Cells in the Living Retina

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