Advanced Age Worsens Phenotypes of Ocular Hypertension in Mice

Glaucoma is a neurodegenerative disorder of the optic nerve and retinal ganglion cells (RGCs) and a major cause of blindness. The two most important risk factors for glaucoma are ocular hypertension (OHT) and advanced age. In this study, we explored the combined impact of aging and OHT on retinal neuronal and microvasculature health. We induced OHT using the bead-injection model in 12 week old (young) and 1.5 year old (old) mice and monitored intraocular pressure (IOP) for 2 weeks. We then explored vascular phenotypes, blood retinal barrier components, RGC counts, and electroretinogram (ERG) changes. Aged mice displayed reduced retinal microvasculature complexity, retinal vascular phenotypes in all three retinal capillary plexi (RCPs), and abnormal ERGs. Aging also impacted basement membrane (BM) and tight junction (TJ) morphology. The impact of OHT was much more evident in old mice; RGC loss was exacerbated, retinal vascular phenotypes were magnified across all three RCPs, and BM and TJ phenotypes were much more severe. However, the impact of OHT on retinal function was unchanged in old mice. Interestingly, the nature of these phenotypes was not equivalent among all RCPs, suggesting regional shared and distinct susceptibilities to aging and OHT. Taken together, aging causes multiple neurovascular phenotypes in mouse retinas, and OHT causes more severe effects in old mice. This suggests an interaction between aging and OHT that may help explain the increased prevalence of glaucoma in older humans.