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Purpose: Recently impaired glycolysis was reported in patients with age-related macular degeneration (AMD) with a high lactate/pyruvate ratio suggesting that increased lactate levels may be implicated in AMD pathogenesis. Elevated serum homocysteine (Hcy)(known as Hyperhomocysteinemia, HHcy) was reported in many AMD clinical studies, suggesting an association between HHcy and the risk of AMD. We reported a direct impact of HHcy on retinal pigment epithelium (RPE) structure, barrier function, and choroidal neovasularization (CNV). We hypothesis that HHcy contributes to AMD via inducing metabolic switch in the mitochondria, in which cells predominantly produce energy by the high rate of glycolysis simulating cancer cells “Warburg” effect, rather than by comparatively low rate of glycolysis followed by oxidation of pyruvate in mitochondria as in normal cells. Increased glycolysis results in an increase …