Uveitis - A Consequence of Failed Ocular Immune Privilege

Uveitis is a condition characterized by intraocular inflammation which can lead to blindness if left untreated; in the US alone, uveitis indeed accounts for ~10% of blindness cases. Importantly, both uveitis and its treatment (typically corticosteroids) can lead to elevated intraocular pressure, which may progress to glaucoma and/or vision loss. It follows that better treatments for uveitis are needed.

While the eye is considered an immune-privileged organ and, to this end, has found ways to both suppress excessive inflammation and maintain tolerance to otherwise immunogenic antigens, uveitis can emerge when immune suppression fails and tolerance breaks down. Our lab is interested in how tolerance is generated and maintained in the eye, as well as how defective tolerance can promote uveitic relapse and disease chronicity. We rely on the experimental autoimmune uveitis (EAU) murine model of uveitis to interrogate chemical and cellular mechanisms of immune suppression and tolerance as well as how tolerance can be maintained over time by specialized subsets of immune-suppressive regulatory T cells (Tregs). A key distinction of our work is that we confirm our mouse findings are relevant to the clinic through interrogating if the same regulatory mechanisms are impaired in uveitis patients. By identifying potently suppressive Treg subsets, we seek to identify cellular alternatives to steroid-based therapy which carries an added risk of visual impairment. We will discuss our findings that synergized melanocortin and adenosinergic signaling to promote Treg generation during EAU and that certain Treg subsets can suppress disease and promote the resolution of intraocular inflammation.

- Summary prepared by Priya Hegde -