TSPO in systemic-ocular immunometabolic crosstalk: mechanisms and therapeutic implications

The eye is increasingly recognized as a tissue shaped by systemic immune and metabolic states rather than an isolated immune-privileged organ. Translocator protein (TSPO), an 18-kDa outer mitochondrial membrane protein enriched in myeloid and glial cells, links mitochondrial homeostasis, redox signaling, lipid metabolism, and immune polarization. This review synthesizes evidence for TSPO involvement in systemic-ocular immunometabolic crosstalk and organizes it into a three-stage working model: peripheral immunometabolic priming, blood-retinal barrier vulnerability, and intraocular glial amplification. We review evidence from systemic autoimmune diseases with ocular manifestations, metabolic diseases with ocular complications, and primary ocular diseases with systemic contributions. We then assess the potential of TSPO as an imaging or fluid biomarker and as a therapeutic target. Current evidence suggests that TSPO is a promising immunometabolic node and underscores the need for cross-organ disease models, cell-specific TSPO manipulation, spatial multi-omics, and local ocular delivery strategies.