Elevated Intraocular Pressure Facilitates T-Cell–Mediated Retinal Ganglion Cell Loss

Purpose: Our previous work indicated that adoptive transfer of CD3⁺ T cells from glaucomatous mice into healthy recipients results in progressive retinal ganglion cell (RGC) loss, providing evidence that adaptive immune responses contribute to glaucoma pathogenesis. This study tested whether elevated intraocular pressure (EIOP) promotes T-cell-mediated RGC degeneration using an adoptive transfer model of autoreactive T cells primed against RGC antigens. Methods: Splenocytes from donor mice that express a green fluorescent protein (GFP)-specific T-cell receptor were transferred into recipient mice expressing GFP in a subset of RGCs. Experimental mice underwent mild IOP elevation; controls remained normotensive or received lipopolysaccharide (LPS). GFP⁺ RGC survival was assessed by fundoscopy and retinal flat mounts. Retinal expression of vascular cell adhesion molecule 1 (Vcam1) was analyzed by immunofluorescence and quantitative PCR. Results: Fundoscopy 8 weeks posttransfer revealed minimal loss of GFP+ RGCs in naive mice (-4.46%), normotensive controls (-2.83%, P = 0.9899), and LPS-treated animals (-4.5%, P > 0.9999). In contrast, EIOP animals lost 18.43% of GFP⁺ RGCs (P = 0.0034) in the central retina. Similar findings were also observed in retinal flat mounts. EIOP retinas also exhibited increased Vcam1 expression associated with retinal capillaries compared with naive controls. Conclusions: These findings indicate that mild EIOP promotes T-cell-mediated degeneration of RGCs, particularly in the central retina. LPS-mediated disruption of the blood-retina barrier alone did not induce RGC loss, indicating that IOP-dependent processes may be required to breach the immune-protective environment of the retina. The increase in Vcam1 expression in EIOP retinas may represent a mechanism facilitating T-cell-mediated retinal neurodegeneration.