Immune Privilege of the Eye: A Delicate Balance Between Clarity and Chaos

PURPOSE: This review aims to describe the key mechanisms behind ocular immune privilege and how disruption of this immunological balance contributes to ocular disease. METHODS: A narrative review of the literature was performed focusing on ocular immune privilege and diseases in which these mechanisms are altered. The review considered evidence related to corneal transplantation, peripheral ulcerative keratitis, age-related macular degeneration, autoimmune uveitis, diabetic retinopathy, ocular tumors, and allergic conjunctivitis. RESULTS: The reviewed literature demonstrates how ocular immune privilege is maintained mainly by a combination of anatomical barriers, local immunomodulatory mediators, regulatory immune-cell interactions, and ACAID-mediated systemic tolerance. Across the ocular conditions reviewed, disease was generally associated with partial disruption, remodeling, or exploitation of these mechanisms rather than complete loss of immuneprivilege. These alterations varied according to the affected ocular compartment and clinical context, but recurrently involved disruption of immune homeostasis, increased inflammatory signaling, altered leukocyte activity, impaired barrier integrity, and reduced local immune restraint. Overall, the evidence supports ocular immune privilege as a dynamic system that is not absolute, preserving ocular homeostasis under normal conditions but contributing to disease when its protective mechanisms are disrupted. CONCLUSIONS: Ocular immune privilege is best understood as a protective but conditional state. Its disruption does not entirely explain most ocular diseases by itself, but it helps illustrate why inflammation, transplantation, tumors, allergy, and other pathologies can behave differently in ocular tissues. Recognizing which elements are preserved or lost in each setting may improve understanding of ocular pathology and support more precise immune-directed approaches.