What Makes Cornea Immunologically Unique and Privileged? Mechanistic Clues from a High-Resolution Proteomic Landscape of the Human Cornea

Success rates of corneal transplantation are particularly high owing to its unique, innate immune privilege derived from a phenomenon known as Anterior Chamber-Associated Immune Deviation (ACAID). Of note, cornea is a transparent, avascular structure that acts as a barrier along with sclera to protect the eye and contributes to optical power. Molecular and systems biology mechanisms underlying ACAID and the immunologically unique and privileged status of cornea are not well known. We report here a global unbiased proteomic profiling of the human cornea and the identification of 4824 proteins, the largest catalog of human corneal proteins identified to date. Moreover, signaling pathway analysis revealed enrichment of spliceosome, phagosome, lysosome, and focal adhesion pathways, thereby demonstrating the protective functions of corneal proteins. We observed an enrichment of neutrophil-mediated immune response processes in the cornea as well as proteins belonging to the complement and ER-Phagosome pathways that are suggestive of active immune and inflammatory surveillance response. This study provides a key expression map of the corneal proteome repertoire that should enable future translational medicine studies on the pathological conditions of the cornea and the mechanisms by which cornea immunology are governed. Molecular mechanisms of corneal immune privilege have broad relevance to understand and anticipate graft rejection in the field of organ transplantation.