**Background:** Translocator protein (TSPO; 18 kDa) is a highly conserved hydrophobic protein located on the outer mitochondrial membrane, involved in cholesterol transport, mitochondrial quality control, calcium homeostasis, and reactive oxygen species (ROS) production. TSPO ligands, both endogenous (e.g., protoporphyrin IX, diazepam-binding inhibitor) and synthetic (e.g., PK11195, Ro5-4864, XBD173, etifoxine), modulate TSPO activity and have shown beneficial effects in central nervous system diseases. However, research on TSPO in ocular diseases has only recently emerged. This narrative review aims to summarize the functional role of TSPO and its ligands in ocular conditions, including age-related macular degeneration (AMD), retinal ischemia, diabetic retinopathy (DR), and glaucoma.
**Methods:** The authors conducted a narrative review of existing literature, summarizing studies on TSPO expression in ocular tissues, its involvement in cellular functions, and the effects of TSPO ligands in in vitro and in vivo models of ocular diseases. Key studies were identified and discussed, with a focus on mechanisms such as steroidogenesis, cholesterol metabolism, inflammation, ROS production, and microglial activation.
**Key Results:** TSPO is highly expressed in retinal pigment epithelium (RPE), choroidal endothelium, Müller cells, and vascular cells, with lower expression in microglia and undetectable levels in retinal neurons. In AMD, TSPO knockout mice exhibit AMD-like features, including impaired cholesterol efflux, increased lipids, and elevated inflammatory factors (IL-1β, TNF-α). TSPO ligands, such as etifoxine, upregulate cholesterol homeostasis genes and promote cholesterol efflux in RPE cells. In a laser-induced choroidal neovascularization (CNV) model, XBD173 inhibits CNV by reducing pro-angiogenic factors (Vegf, Ang1, Ang2) and promoting microglial transition to neuroprotective phenotypes. In retinal ischemia, XBD173 reduces neuron death, decreases microglial number, and promotes M2 phenotype transformation, while also increasing diazepam-binding inhibitor levels in Müller cells. In DR, TSPO is downregulated in rat models of type-2 diabetes 12 weeks after disease modeling, but upregulated in peripheral blood of diabetic patients, with higher levels in active proliferative DR. TSPO ligands (Ro5-4864, PK11195) reduce glucose levels in zebrafish larvae and protect against metabolic disorders in type-2 diabetes rat models. In glaucoma, TSPO is upregulated under elevated pressure (75 mmHg) and colocalizes with allopregnanolone (AlloP) and 5α-reductase in retinal ganglion cells (RGCs). PK11195 promotes TSPO expression and inhibits pressure-induced RGC apoptosis via the TSPO-5αRD-AlloP pathway.
**Clinical Implications:** TSPO represents a promising therapeutic target for multiple ocular diseases, with ligands showing potential to modulate cholesterol metabolism, reduce oxidative stress, suppress inflammation, and regulate microglial activation. However, the review highlights several limitations: TSPO expression in ocular surface tissues, lens, lacrimal gland, and optic nerve remains unexplored; the essential role of TSPO in healthy ocular tissue is unclear; and comprehensive evaluation of adverse effects of TSPO ligands in the ocular environment is lacking. Further studies are needed to validate these findings and translate them into clinical applications.