Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin.
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.
Carroll
Joseph
J
Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. jcarroll@mcw.edu
Baraas
Rigmor C
RC
Wagner-Schuman
Melissa
M
Rha
Jungtae
J
Siebe
Cory A
CA
Sloan
Christina
C
Tait
Diane M
DM
Thompson
Summer
S
Morgan
Jessica I W
JI
Neitz
Jay
J
Williams
David R
DR
Foster
David H
DH
Neitz
Maureen
M
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics*; D001120:Arginine / Q000235:genetics; D002452:Cell Count; D041321:Chromosomes, Human, X / Q000235:genetics; D055253:Color Vision / Q000235:genetics; D055358:Cone Opsins / Q000235:genetics*; D003545:Cysteine / Q000235:genetics; D003941:Diagnostic Techniques, Ophthalmological; D005260:Female; D006801:Humans; D008297:Male; D009030:Mosaicism; D009154:Mutation / Q000235:genetics*; D012160:Retina / Q000473:pathology; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology; D055815:Young Adult
D055358:Cone Opsins; D001120:Arginine; D003545:Cysteine