Albinism, an inherited disorder of melanin biosynthesis, disrupts normal retinal development, with foveal hypoplasia as one of the more commonly associated ocular phenotypes. However the cellular integrity of the fovea in albinism is not well understood – there likely exist important anatomical differences that underlie phenotypic variability within the disease and that also may affect responsiveness to therapeutic intervention. Here, using spectral domain optical coherence tomography (SD-OCT) and adaptive optics (AO) retinal imaging, we obtained high-resolution images of the foveal region in six individuals with albinism. We provide a quantitative analysis of cone density and outer segment elongation demonstrating that foveal cone specialization is variable in albinism. In addition, our data reveal a continuum of foveal pit morphology, roughly aligning with schematics of normal foveal development based on post-mortem analyses. Different albinism subtypes, genetic mutations, and constitutional pigment background likely play a role in determining the degree of foveal maturation.
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...
The HRR pseudoisochromatic plate (pip) test was originally designed as a screening and diagnostic test for color vision deficiencies. The original HRR test is now long out of print. We evaluate here the new 4th edition of the HRR test, produced in 2002 by Richmond Products. The 2002 edition was compared to the original 1955 edition for a group of subjects with normal color vision and a group who had been previously diagnosed as having color vision deficiencies. The color deficient subjects spanned the range of severity among people with red-green deficiencies except for one individual who had a mild congenital tritan deficiency. The new test compared favorably with the original and in at least two areas, outperformed it. Among subjects with deutan defects the classification of severity correlated better with the anomaloscope results than the original; all the subjects who were classified as dichromats on the anomaloscope were rated as "severe" on the new HRR, while those diagnosed as anomalous trichromats were rated as mild or medium on the new test. Among those with moderate and severe defects the new test was highly accurate in correctly categorizing subjects as protan or deutan. In addition, a mild tritan subject made a tritan error on the new test whereas he was misdiagnosed as normal on the original.
Aims To examine the practical improvement in image quality afforded by a broadband light source in a clinical setting and to define image quality metrics for future use in evaluating spectral domain optical coherence tomography (SD-OCT) images. Methods A commercially available SD-OCT system, configured with a standard source as well as an external broadband light source, was used to acquire 4 mm horizontal line scans of the right eye of 10 normal subjects. Scans were averaged to reduce speckling and multiple retinal layers were analysed in the resulting images. Results For all layers there was a significant improvement in the mean local contrast (average improvement by a factor of 1.66) when using the broadband light source. Intersession variability was shown not to be a major contributing factor to the observed improvement in image quality obtained with the broadband light source. We report the first observation of sublamination within the inner plexiform layer visible with SD-OCT. Conclusion The practical improvement with the broadband light source was significant, although it remains to be seen what the utility will be for diagnostic pathology. The approach presented here serves as a model for a more quantitative analysis of SD-OCT images, allowing for more meaningful comparisons between subjects, clinics and SD-OCT systems.
The topographical distribution of relative sensitivity to red and green lights across the retina was assayed using a custom-made wide-field color multifocal electroretinogram apparatus. There were increases in the relative sensitivity to red compared to green light in the periphery that correlate with observed increases in the relative amount of long (L) compared to middle (M) wavelength sensitive opsin mRNA. These results provide electrophysiological evidence that there is a dramatic increase in the ratio of L to M cones in the far periphery of the human retina. The central to far peripheral homogeneity in cone proportions has implications for understanding the developmental mechanisms that determine the identity of a cone as L or M and for understanding the circuitry for color vision in the peripheral retina.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.