Targeting Galectin-3 for neuroprotection in glaucoma

Background: Neuroinflammation and metabolic disruption are critical early components of glaucoma. I have identified that Galectin-3 (Gal-3), a pro-inflammatory protein, is increased early in glaucoma. Emerging evidence suggests that Gal-3 may be a key actor which orchestrates these two disease components, and we have demonstrated that blocking Gal-3 provides robust neuroprotection in glaucoma. However, its mechanisms of action remain unresolved. This project will develop the understanding necessary for clinical translation of Gal-3 targeting therapies in glaucoma.

Issue: Despite treatment, many glaucoma patients continue to lose vision supporting the need for true neuroprotective therapies. FDA approved Gal-3 inhibitors exist for other diseases, with better knowledge of the role of Gal-3 in the retina and glaucoma we can validate the potential of moving Gal-3 inhibition toward clinical trials for glaucoma.

2-year workplan: (1) Identify mechanism by which Gal-3 drives neuroinflammation in glaucoma; (2) Elucidate how Gal-3 intersects inflammation and metabolic dysfunction. We will achieve this using: (1) proteomics and transcriptomics to identify binding partners and effectors of Gal-3; (2) bioluminescent metabolic assays, metabolomics, and metabolic signalling arrays following Gal-3 modulation.

Meaning: Gal-3 inhibitors are prime candidates to re-purpose for neuroprotection in glaucoma.