{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nInterphotoreceptor retinoid‐binding protein (IRBP) plays a critical role in maintaining immune tolerance in the eye. Studies have demonstrated that thymic expression of IRBP is important for deleting autoreactive T cells, and lack of its expression can predispose to organ‐specific autoimmunity such as autoimmune uveitis. In murine models, loss or altered presentation of IRBP dramatically shifts T‐cell epitope recognition and can result in an exacerbated inflammatory response mediated in part by γδ T cells. These findings indicate that IRBP functions as a key endogenous self‐antigen that sets the threshold for immune activation against retinal tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its immunologic role, IRBP is essential for proper visual function. Secreted by photoreceptors into the interphotoreceptor matrix, it serves as a transport protein for retinoids—including the critical 11‐cis‐retinol and 11‐cis‐retinal—thereby facilitating the visual cycle, preserving the integrity of photoreceptor cells (especially cones), and protecting their isomeric state under light conditions. Disruption of IRBP function or mutations that impair its secretion can lead to a retinoid deficiency, triggering cellular stress and contributing to progressive retinal degeneration. This multifaceted role in retinoid delivery and photoreceptor survival underscores its significance in cone‐specific visual pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its primary roles in immune regulation and retinoid trafficking, IRBP is also implicated in retinal cell homeostasis and intercellular communication. Its expression is modulated by external signals from Müller cells and is essential for normal retinal development and protection against degenerative processes. Notably, experimental models have shown that IRBP deficiency may be associated with not only retinal degeneration but also with refractive errors in the developing eye, while in other contexts, loss of IRBP per se does not predispose photoreceptors to oncogenic transformation. Together, these studies suggest that IRBP integrates developmental, metabolic, and stress‐related signals to maintain retinal structure and function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jason DeVoss, Yafei Hou, Kellsey Johannes, et al. 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