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A key event is the blood-retinal barrier disruption, with loss of pericytes and endothelial cells, leading to microaneurysms, increased vascular permeability, and capillary obstruction, resulting in poor oxygen distribution in the retina (Wang and Lo, 2018

Cells import cystine from the blood, reconvert it to cysteine (likely using ascorbate as cofactor), and from it synthesize GSH

After adding 800 L of cold MeOH/H2O to the frozen tissue, a pellet pestle (Sigma-Aldrich, UK) was used to homogenize the tissue for 1 min

Thus, when drugs are applied topically, their local bioavailability is reduced, as expected

But the mechanistic rationale is strong, the safety profile appears favorable, and the early observational data aligns with what the biochemistry predicts