Abstract
Purpose :
Intrinsically photosensitive retinal ganglion cells (ipRGCs) represent a third class of photoreceptors in the retina. These ipRGCs mediate several non-image-forming visual functions, including regulation of pupillary light reflex, light aversion and light entrainment of circadian rhythms. Aging has a significant impact on visual function which includes changes in sleep and circadian regulatory mechanisms. Therefore, we have evaluated age-related alterations of the morphological changes of ipRGCs in mice and correlated them with their associated behavioral dysfunctions at 6 and 12 months old.
Methods :
Female and male C57BL/6J mice were used for this study. The behavioral consequences of aging were studied in a large cohort of mice using newly acquired and mined data for pupillary light reflex and light aversion, and in a smaller cohort of mice using newly acquired visual acuity and contrast sensitivity. Immunohistochemistry in mouse retinal wholemounts stained with antibodies against ipRGCs were used to study their morphology. Morphological analysis included Sholl analysis, number of branch points and dendritic length.
Results :
Morphological analysis showed that ipRGC dendritic field complexity were remarkably stable with ageing in male and female animals. Similarly, the pupillary light reflex and visual acuity were stable with ageing and across sex. By contrast, alterations were observed in contrast sensitivity at the lowest spatial frequency tested, and in light aversion distinct from the pupillary light reflex.
Conclusions :
With ipRGC morphology and function preserved during aging, the ipRGC circuitry might be a putative biomarker in diseases where the loss of ipRGCs has been reported such as Alzheimer’s, Parkinson’s disease and glaucoma.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.