Investigation of immune checkpoint receptor activation as a strategy for treating retinal inflammation.

The proposed DPhil project will investigate immune checkpoint receptor signalling in the eye and target these pathways to control retinal inflammation in mouse models of uveitis. Checkpoint receptors are surface proteins on immune cells which, when bound by their cognate ligands, inhibit activation of the immune cells. Retinal transcriptomic data indicate native expression of checkpoint ligands to PD-1, BTLA, TIGIT and CD200R, thus implicating these pathways in ocular immune tolerance. Moreover, immune checkpoint receptor inhibitors used in cancer therapy are known
to cause uveitis3. Therefore, we hypothesise that immune checkpoint activation could promote restoration of ocular immune homeostasis during intraocular inflammation.

Results from this DPhil project will provide insights into immune checkpoint receptor-ligand dynamics in retinal inflammation and whether their signalling axes can be exploited for targeted suppression of neuroinflammation in the eye. While initial tests will be focused on uveitis, these insights will be relevant to a wide range of retinal and neuroinflammatory diseases where imbalance of local immune tolerance play pathogenic roles.