AIBP: A New Safeguard against Glaucomatous Neuroinflammation

Glaucoma is a group of ocular diseases that causes irreversible blindness worldwide and is characterized by a multifactorial degeneration of optic nerve and retinal ganglion cells (RGCs), leading to vision loss. One of the significant risk factors in glaucoma pathogenesis is glia-driven neuroinflammation. Impairment of mitochondrial dynamics and bioenergetics is associated with glaucomatous neurodegeneration and is linked to neuroinflammation. Apolipoprotein A-I binding protein (AIBP) binds to toll-like receptor 4 (TLR4) and facilitates the removal of excess cholesterol from the plasma membrane in activated cells, suggesting the regulation of cholesterol-driven inflammation by inhibiting the TLR4-associated lipid rafts. AIBP is localized in mitochondria and regulates mitophagy by ubiquitination of mitofusin 1 and 2. We observed elevated intraocular pressure-induced AIBP deficiency in glaucomatous neurodegeneration. We also observed that AIBP deficiency activated TLR4 in Müller glia, triggered mitochondrial dysfunction in both RGCs and Müller glia and impaired visual function. In mouse models of glaucoma, AIBP treatment protects RGCs by reducing inflammatory responses. Here, our review focuses on investigating the role of AIBP in the retina and examining the underlying mechanism by which AIBP contributes to the pathogenesis of glaucoma, aiming to provide new insight into the therapeutic potential for the treatment of glaucoma.