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

• DOI: 10.1016/j.ajpath.2020.04.011
• Publication Date: 2020-05-08T01:38:11Z
• Authors: Thi Hong Khanh Vu; Huihui Chen; Li Pan; Kin-Sang Cho; Djoeke Doesburg; Eric F. Thee; Nan Wu; Elisa Arlotti; Martine J. Jager; Dong Feng Chen
• Keywords: CD4-Positive T-Lymphocytes; Retinal Ganglion Cells; 0301 basic medicine; Retinal Degeneration; Retinal Vessels; 551; Adoptive Transfer; Retina; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Retinal Diseases; Ischemia; Disease Progression; Animals

Retinal ischemic events, which result from occlusion of the ocular vasculature share similar causes as those for central nervous system 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 the exact roles remain elusive. We found that acute ischemia-reperfusion injury to the retina induced a prolonged phase of retinal ganglion cell loss that continued to progress during 8 weeks after the procedure. This phase was accompanied by microglial activation and CD4+ T-cell infiltration into the retina. Adoptive transfer of CD4+ T cells isolated from diseased mice exacerbated retinal ganglion cell loss in mice with retinal reperfusion damage. On the other hand, T-cell deficiency or administration of T-cell or interferon-γ-neutralizing antibody attenuated retinal ganglion cell degeneration and retinal function loss after injury. These findings demonstrate a crucial role for T-cell-mediated responses in the pathogenesis of neural ischemia. These findings point to novel therapeutic targets of limiting or preventing neuron and function loss for currently untreatable conditions of optic neuropathy and/or central nervous system ischemic stroke.