Abstract
Purpose :
Previous studies indicate the presence of gliotic and neuroinflammatory changes in the unaffected optic nerve of unilateral injury models. The purpose of this study was to systematically examine the contribution of injury, IOP, and excitotoxicity stressors to this contralateral gliotic phenotype in mice with unilateral retinal ganglion cell (RGC) degeneration.
Methods :
Using a dual model approach, we compared IOP-dependent gliosis and IOP-independent gliosis in the microbead model of ocular hypertension and the NMDA model of excitotoxicity. To delineate the contributions of ocular hypertension and ocular injury to contralateral gliosis in the optic nerve, we performed three, unilateral variations of the microbead occlusion model: sham injection, saline injection and microbead injection. Reactive gliosis was assessed by immunohistochemical approaches and quantitative digital analysis of microglia and astrocyte reactivity, including hypertrophy, ramification, and density. Gliosis measures were benchmarked to the neurodegeneration profile of each optic nerve as well as outcomes of visual function, including electroretinogram (ERG) and flash visual-evoked potentials (F-VEP).
Results :
RGC degeneration was observed at both structural and functional levels of affected eyes following 4 weeks of either microbead-induced IOP elevation or NMDA excitotoxicity. Attenuation of ERG and F-VEP amplitudes were detected in microbead-injected and NMDA-injected eyes (p<0.05). However, visual function contralateral to these stressors remained unchanged from naïve levels (p>0.05). Similar outcomes were noted for RGC and axon pathology, where only microbead-injected and NMDA-injected eyes exhibited changes in degenerative axon profiles (p<0.05). In contrast, quantification of percent area coverage (hypertrophy/ramification), nearest neighbor analysis (migration), and density measurements indicated increased microglia reactivity (p<0.05) and astrocyte remodeling (p<0.05) in both affected and contralateral optic nerves. Contralateral gliosis was not noted in optic nerves control, sham, and saline-injected animals (p>0.05).
Conclusions :
Our results suggest that contralateral gliosis is not a generalized response to ocular stress or injury, but coincides with RGC degeneration. Furthermore, contralateral gliosis is apparent in both microglia and astrocyte populations, similar to the gliosis response in nerve with active axon degeneration.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.