A groundbreaking study from the Shiley Eye Institute and Viterbi Family Department of Ophthalmology has unveiled a promising gene therapy strategy to combat glaucoma, a leading cause of irreversible blindness worldwide.

Wonkyu Ju, PhD, Professor and the Hanna and Mark Gleiberman Chancellor’s Endowed Chair in Glaucoma Research, and his research team have identified a pivotal role for apolipoprotein A-I binding protein (AIBP) in protecting retinal ganglion cells (RGCs) and Müller glial cells. Their findings demonstrate that AIBP regulates cholesterol levels and suppresses harmful inflammation—two critical drivers of glaucoma progression.

In retinal tissues from glaucoma patients and mouse models of glaucoma, AIBP levels were found to be significantly reduced. This deficiency led to abnormal cholesterol accumulation, RGC degeneration, and optic nerve damage. To counter these effects, the team administered AAV-AIBP via a single gene therapy injection directly into the glaucomatous eye of a mouse. The treatment successfully restored cholesterol homeostasis, reduced inflammation, promoted RGC survival, and preserved Müller glial cells—ultimately protecting vision.

“These experimental studies indicate that restoring AIBP expression in the glaucomatous retina reduces neuroinflammation and protects RGCs and Müller glia, suggesting the therapeutic potential of AAV-AIBP in human glaucoma,” said Dr. Ju.

Co-author Robert N. Weinreb, MD, Distinguished Professor and Chair of the Viterbi Family Department of Ophthalmology, added, “With this pioneering approach, a step is taken toward a durable, disease-modifying treatment for glaucoma—moving beyond traditional management.”

This project represents a collaborative effort harnessing the expertise and resources of UC San Diego, RAFT Pharmaceuticals, and the NIH Blueprint Neurotherapeutics Network – Biologic. The study was partially supported by R01 and UG3 grants from the National Institutes of Health (NIH), which fund the development of innovative gene therapies aimed at reducing retinal neuroinflammation and delivering neuroprotection for patients affected by glaucoma.

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