Spatial and temporal expression of short, long/medium, or both opsins in human fetal cones

Human cone photoreceptors are characterized by long (L), medium (M), or short (S) wavelength‐specific opsin. No reports have described the developmental pattern of human cone opsin expression, nor has the existence of human cones containing more than one opsin been tested. Single‐and double‐label immunocytochemistry and in situ hybridization have been used to determine the developmental pattern of opsin appearance and to investigate the presence of double‐labeled cones in sections and wholemounts of human fetal, neonatal, infant, and adult retina. S opsin protein appears in and around the fovea at fetal week (Fwk) 10.9, whereas L/M opsin first appears in the fovea at Fwk 14–15. S opsin mRNA and protein are consistently detected much farther into peripheral retina than L/M opsin, indicating that S appears before L/M opsin. S cones cover 90% of the retina by Fwk 19. L/M cones appear outside the central retina by Fwk 21.5 and reach the retinal edge by Fwk 34–37. The spatial pattern of mRNA expression closely matches that for protein, but mRNA appears slightly earlier than protein at a given retinal point, indicating that only short delays occur between mRNA expression and translation into protein. Cones containing both S and L/M opsin (S+L/M) appear around the fovea shortly after L/M opsin is expressed, are found in more peripheral retina at older ages, and decrease in number after birth. Some S+L/M cones are still detected in adult retina. Both S opsin protein and mRNA appear significantly earlier than L/M mRNA or protein across the human retina, suggesting that the two cone types differentiate under independent controlling factors. However, the presence of single cones containing both S and L/M opsin during development suggests that human cones can respond to the factors controlling expression of each opsin. J. Comp. Neurol. 425:545–559, 2000. © 2000 Wiley‐Liss, Inc.