Abstract
Purpose :
Early in glaucoma astrocytes protect the retinal ganglion cells (RGCs). Here we tested the hypothesis that the astrocytes are responsible for driving the antioxidant response that counteracts intraocular pressure (IOP) elevation induced oxidative stress.
Methods :
Adeno-associated viral vectors directed to either astrocytes or RGCs and driving expression of Cre (or tdTomato alone) were intravitreally injected into Nrf2 floxed mice. Two weeks later the mice were intracamerally injected with microbeads to elevate IOP. Two weeks after IOP elevation we measured levels of antioxidant enzymes, reactive oxygen species, visual function, and optic nerve histology. Additional mice were intravitreally injected with AAV2/2.pSncg.Nrf2 (or tdTomato) to transduce the RGCs. Two weeks later they underwent microbead occlusion and five weeks later visual function and optic nerve structure were assessed.
Results :
Decreasing Nrf2 levels in either cell type blocked the antioxidant response and resulted in earlier onset vision loss based on the photopic negative response and visual evoked potentials, and greater axon degeneration in the optic nerve. Over-expression of Nrf2 in the RGCs decreased reactive oxygen species and protected against glaucoma pathology.
Conclusions :
Both astrocytes and RGCs contribute to the IOP elevation induced antioxidant response. Increasing levels of Nrf2 in the RGCs enhances the efficacy of the endogenous antioxidant response and is protective.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.