retinaldehyde and Albinism

Retinaldehyde adducts (bisretinoids) accumulate in retinal pigment epithelial (RPE) cells as lipofuscin. Bisretinoids are implicated in some inherited and age-related forms of macular degeneration that lead to the death of RPE cells and diminished vision. By comparing albino and black-eyed mice and by rearing mice in darkness and in cyclic light, evidence indicates that bisretinoid fluorophores undergo photodegradation in the eye (Ueda et al. Proc Natl Acad Sci 113:6904-6909, 2016). Given that the photodegradation products modify and impair cellular and extracellular molecules, these processes likely impart cumulative damage to retina.

Topics: Albinism; Amines; Animals; Antioxidants; ATP-Binding Cassette Transporters; Darkness; Eye Color; Free Radical Scavengers; Light; Lipofuscin; Macular Degeneration; Melanosis; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Photochemistry; Retinal Pigment Epithelium; Retinaldehyde; Rod Cell Outer Segment; Stargardt Disease; Vitamin E

We have measured the sensitivity of rod photoreceptors isolated from overnight dark-adapted mice of age P12 (neonate) through P45 (adult) with suction-pipette recording. During this age period, the dark current increased roughly in direct proportion to the length of the rod outer segment. In the same period, the flash sensitivity of rods (reciprocal of the half-saturating flash intensity) increased by approximately 1.5-fold. This slight developmental change in sensitivity was not accentuated by dark adapting the animal for just 1 h or by increasing the ambient luminance by sixfold during the prior light exposure. The same small, age-dependent change in rod sensitivity was found with rat. After preincubation of the isolated retina with 9-cis-retinal, neonatal mouse rods showed the same sensitivity as adult rods, suggesting the presence of a small amount of free opsin being responsible for their lower sensitivity. The sensitivity of neonate rods could also be increased to the adult level by dark adapting the animal continuously for several days. By comparing the sensitivity of neonate rods in darkness to that of adult rods after light bleaches, we estimated that approximately 1% of rod opsin in neonatal mouse was devoid of chromophore even after overnight dark adaptation. Overall, we were unable to confirm a previous report that a 50-fold difference in rod sensitivity existed between neonatal and adult rats.

Topics: Aging; Albinism; Animals; Animals, Newborn; Dark Adaptation; Diterpenes; Light; Membrane Potentials; Mice; Mice, Inbred C57BL; Photic Stimulation; Rats; Rats, Sprague-Dawley; Retina; Retinaldehyde; Rod Cell Outer Segment; Rod Opsins; Time Factors