{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:16:56Z","timestamp":1793305016910,"version":"4.5.0"},"reference-count":151,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The retina preserves vision by tightly regulating inflammation (\u201cimmune privilege\u201d) via blood\u2013retinal barriers, neuroglial checkpoints, and tolerogenic cues. This actively maintained\u2014and potentially restorable\u2014state is breached in major retinal diseases through three recurrent archetypes. We synthesize 2015\u20132025 advances into a framework of barrier failure, innate dysregulation, and adaptive autoimmunity. Across age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), and non-infectious uveitis (NIU): AMD exhibits complement\u2013microglia para-inflammation with later outer-barrier compromise; DR exemplifies inner-BRB failure with inflammatory amplification; RP begins with degeneration-triggered innate activation and progresses to combined innate\u2013adaptive injury; NIU represents T-cell-driven breach of the blood\u2013retinal barrier. Interventional human evidence supports immunity as a therapeutic target: complement inhibition slows geographic atrophy; anti-VEGF reduces leak; intravitreal corticosteroids suppress inflammatory edema; and anti-TNF\/IL-6R improve refractory NIU. Emerging strategies aim at privilege restoration\u2014reinforcing myeloid checkpoints, tempering inflammasomes, and exploring tolerance-oriented approaches to re-educate adaptive immunity. Evidence from preclinical and early translational studies indicates that ocular tissues can imprint regulatory\/anergic programs on pathogenic T cells, supporting mechanism-aligned, patient-tailored immunotherapy as a testable route to restore regulation, mitigate inflammation, and slow degeneration.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1703382","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T05:13:40Z","timestamp":1764220420000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Breach and restoration of retinal immune privilege: barrier failure, innate dysregulation, and adaptive autoimmunity"],"prefix":"10.3389","volume":"16","author":[{"given":"Qiwei","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1102574","article-title":"Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation","volume":"74","author":"Streilein","year":"2003","journal-title":"J Leukoc Biol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1111\/j.1600-065X.2006.00439.x","article-title":"Ocular autoimmunity: the price of privilege","volume":"213","author":"Caspi","year":"2006","journal-title":"Immunol Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3109\/02713689208999545","article-title":"Identification of 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