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Jennifer Lee Kielczewski, Reiko Horai, Rachel R. Caspi; Naïve retina-specific T cells provide neuroprotection to retinal ganglion cells in mouse models of glaucoma. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3298.
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© ARVO (1962-2015); The Authors (2016-present)
T cells that recognize central nervous system antigens can elicit autoimmune disease, but when properly controlled they also can mediate neuroprotection (“beneficial autoimmunity”). We examined whether naive autoreactive T cells from R161H mice that express a T cell antigen receptor specific to the retinal antigen, Interphotoreceptor Retinoid Binding Protein (IRBP), provide neuroprotection to retinal ganglion cells (RGC) after glutamate or optic nerve crush (ONC) injury.
Purified naive CD4+ T cells were obtained from R161H donor mice genetically marked with eGFP. Wild type recipients received ~2M adoptively transferred R161H T cells and control mice received the same number of polyclonal control T cells. Mice underwent fluorogold labeling of RGC prior to cell transfer and then subjected to chemical-induced injury by intravitreal injection of glutamate (400nM) or by mechanical-induced ONC injury to one eye. Mice were sacrificed 4 or 7 days after injury. Flatmounted retinas were imaged for quantification of RGC. Retinas were also cryosectioned for microscopy analysis of eGFP+ cell localization in the retina.
At 4 days, mice (n=8) with ONC injury experienced a significant 20% less RGC loss compared to mice infused with control polyclonal T cells (p<0.05). At 1 week, glutamate injured mice (n=8) experienced a neuroprotective effect with a significant 30% reduction in RGC loss compared to control mice (p<0.05). The difference in kinetics of the neuroprotection may be attributed to the number of eGFP+ cells entering into the eye, which may be affected by location of the antigen for the IRBP specific T cells relative to the site of injury. In glutamate injured mice, where RGCs undergo direct injury in close proximity to the location of the antigen recognized by the T cells, a higher frequency of eGFP+/CD4+ cells were present in the retina, specifically near the RGC layer, where they persisted 1 week post injury. In ONC injured mice, where the optic nerve is far from the site of the antigen recognized by the T cells, fewer eGFP+/CD4+ cells were detected in the retina, as well as the optic nerve, and the T cells didn’t persist beyond 4 days in the eye.
Exogenously administered naive retina-specific CD4+ T cells can enter into the retina to mediate neuroprotection of injured RGCs. Kinetics of neuroprotection may vary depending on the site and type of injury.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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