Constitutive Neuronal Expression of the Immune Regulator, Programmed Death 1 (PD-1), Identified During Experimental Autoimmune Uveitis

Purpose: Programmed death-1 (PD-1) ligation downregulates active lymphocyte responses. The authors tested whether PD-1 or its ligands are expressed in the posterior segment during active intraocular inflammation. Methods: Experimental autoimmune uveitis (EAU) was induced using interphotoreceptor retinoid-binding protein (IRBP 161-180). Ocular inflammation was evaluated by histology and expression of PD-1 ligand tested by immunohistochemistry. PD-1 expression was evaluated by immunohistochemistry, RT-PCR, and Western immunoblotting. Results: Using immunohistochemistry, PD-1, but not its ligands, was constitutively expressed in retinal neurons of naive mouse retina. Both PD-1 and its ligands were observed, as expected, in sites of active inflammation. Conclusions: PD-1 and its ligands were expressed in sites of active inflammation, in accordance with many other models of inflammatory disease. Surprisingly, PD-1, not previously described outside the immune system, was constitutively expressed in retinal neurons, raising the possibility that PD-1 signaling may be important for neuronal function in the absence of an inflammatory insult.