Degeneration of Melanopsin Photosensitive Ganglion Cells in Human Retinas With Aging and in Animal Models of Retinitis Pigmentosa

Abstract

Purpose: : In the mammalian retina, besides the rods and cones another photoreceptor type has been discovered that corresponds to a population of ganglion cells. These ganglion cells express the photopigment melanopsin, and carry out the regulation of the circadian rhythm and the pupillary reflex. The aim of this study was to investigate in humans the age related changes of the melanopsin ganglion cells. Furthermore, we studied morphological changes in these cells in two models of retinitis pigmentosa, the P23H rat and the C3H mouse.

Methods: : For this study we used homozygous P23H line 3 rats aged between 4 and 18 months. Sprague-Dawley (SD) were used as controls. C3H mice were also used rd/rd aged between 1 and 7 months, and controls +/+. Human retinas were studied at prenatal P115 and at 10 and 53 years old. Whole retinas were stained by immunohistochemical technique with avidin-biotin complex (ABC) and immunofluorescence. Melanopsin cells from each retina were drawn using a camera lucida. Quantification and morphometric analysis were carried out using the software NIH Image J.

Results: : In human retina, expression of melanopsin was found at prenatal P115, being located in the cell bodies of some ganglion cells. In the studied human eyes a decrease of the density of melanopsin cells was observed (≈44.5%) with the age from 10 to 53 years old. In the P23H rat there was a decrease of melanopsin ganglion cells around 74% at 18 months of age, while no significant changes were observed in the SD rats. The C3H rd/rd mice showed also a decrease approximately 50% of the melanopsin cells at seven months old.Changes in dendritic arborization in melanopsin neurons were found in P23H rat retina with aging.

Conclusions: : The number of melanopsin cells decrease with age in human retina, hovewer no change were found in SD rat and C3H mice. However more human eyes need to be studied to confirm these observations. There is also a drastic loss of these cells with the progression of the disease in the two studied models of retinitis pigmentosa.

Keywords: ganglion cells • circadian rhythms • retinal degenerations: cell biology