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AE Hendrickson, E Cornish, M Xiao, J Provis; The Role of Opsin Coexpression and Apoptosis in Determining Cone Types in the Developing Human Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):828.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Cones expressing both short (S)- and long or medium (L/M)-wavelength sensitive opsin are present in fetal human retina. This study tracks the temporal and spatial pattern of these S+L/M cones to adulthood. Because S+L/M cones are rare in adults, this decline could be due to programmed cell death or a transformation into another photoreceptor type. Methods: Sections and wholemounts of human retina from fetal week (Fwk) 13 to adult were stained for double label immunocytochemistry, followed by TUNEL labeling to detect apoptotic nuclei. The number of S, L/M and S+L/M cones were counted using standard microscopic or confocal methods. Results: S+L/M cones were not detected before L/M opsin appeared in the fovea at Fwk15. The highest number of S+L/M cones consistently was at the front of L/M opsin expression with few detected in more central retina. At birth this front was near the retinal edge and 10% of the cones were S+L/M, but by 8mo in the same region, only 0.03% cones were S+L/M. In older retinas S+L/M cones showed no apparent pattern, and were less than 0.01% of total cones. There was no increase in TUNEL labeling in cones behind the L/M opsin expression front in fetal retina. S cone density near the optic disc dropped 3fold just before and during L/M opsin expression in this region. This was not due to apoptosis because S cones showed no increase in TUNEL labeling during the period. An S cone "switch" via an intermediate S+L/M state to L/M cones also was ruled out because counts of the percentage of S cones, using alpha-transducin to mark putative L/M cones, showed that S cones remained at 7.5-9% at all ages. Conclusion: We found no evidence for selective S+L/M cone death during development, suggesting that the drop in their number is due to most becoming L/M cones in adult retina.The stable percentage of S cones and low level of TUNEL labeling in all cones over a wide range of ages means that apoptosis does not play a major role in determining the proportion of S vs L/M cones during development. The transient presence of S opsin during L/M opsin expression seems to be a common, but unexplained process.
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