PROJECT SUMMARY/ABSTRACT Uveitis is a heterogenous group of ocular inflammatory diseases that results in significant ocular morbidity and can cause long-term blindness if not diagnosed accurately and treated adequately. A major challenge in uveitis, however, is the inadequate clinical and laboratory methods to determine the exact cause of the inflammatory response. Furthermore, biomarker discovery is lacking in uveitis. Here, we propose to leverage programmable phage display peptidomes coupled with high-throughput sequencing to identify autoantigens and antibodies important for uveitis. In Aim 1, we will use a comprehensive human peptidome phage display library to bio-pan for autoantigens in the intraocular fluid and tear specimens of patients with idiopathic anterior uveitis. In Aim 2, we will generate a comprehensive viral peptidome phage library to agnostically bio-pan for viral antibodies in the intraocular fluid and plasma specimens of patients with presumed viral-associated anterior uveitis but for whom conventional diagnostics failed to reveal an etiology. Viral and human peptidomes have not been applied to the intraocular fluid and tears of uveitis patients. We anticipate these experiments will result in new diagnostics for uveitis and thus have the potential to improve patient care and clinical outcomes.