CD4+ T Cell Responses Mediate Progressive Neurodegeneration in Experimental Ischemic Retinopathy.

Abstract Retinal ischemic events as a result of occlusion of the ocular vasculature share similar etiologies of central nervous system (CNS) stroke and are among the most common cause of acute and irreversible vision loss in elderly patients. Currently, there is no established treatment, and the condition often leaves patients with seriously impaired vision or blindness. The immune system, particularly T cell-mediated responses, is thought to be intricately involved, but their exact roles remain elusive. Here we showed that acute ischemia/reperfusion injury to the retina induced a prolonged phase of retinal ganglion cell (RGC) loss that continued to progress over 8 weeks post procedure. This was accompanied by microglial activation and CD4+ T cell infiltration into the retina. Adoptive transfer of CD4+ T cells isolated from diseased mice exacerbated RGC loss in mice with retinal reperfusion damage. Whereas, T cell deficiency or administration of T cell or interferon-γ neutralizing antibody attenuated RGC degeneration and retinal function loss after injury. These findings demonstrate a crucial role for T cell-mediated responses in the pathogenesis of neural ischemia. They point to novel therapeutic targets of limiting or preventing neuron and function loss for currently untreatable conditions of optic neuropathy and/or CNS ischemic stroke.