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Retinal degenerative diseases are the leading causes of blindness and low vision among working-age and older adults worldwide, with 170 and 130 million individuals suffering from age-related macular degeneration (AMD) and diabetic retinopathy, respectively. Although several studies began to show benefits from dietary interventions against retinal degenerative disease, an integrated approach is needed to understand molecular mechanisms underpinning the protective or risky effect of dietary factors. A specific area of research that elucidates mechanisms involved in gene-diet interaction is the Nutri-epigenomics, the study of the impact of diet on gene expression by modulating epigenetic mechanisms. The present research investigated the role of DNA methylation – one of the most commonly analysed epigenetic mechanisms — in the pathophysiology of retinal degenerative diseases, by exploiting a multiple integrated approach. In vitro studies initially helped us to understand how pathological features of retinal degeneration (e.g. oxidative stress, inflammation and hyperglycaemia) modulated functions of enzymes involved in the methylation of Long Interspersed Nuclear Element 1 (LINE1) sequences in retinal cells. We also proved that some nutrients (e.g. resveratrol and curcumin) might counteract these effects and restore DNA methylation level in retinal cells under oxidative, inflammatory and high glucose conditions. We further analysed whether LINE-1 methylation level differed between patients with AMD and controls without posterior segment eye diseases. Interestingly, we noted a significant difference between the two groups, with higher LINE-1 methylation level in blood samples from AMD patients. This evidence —albeit promising for biomarker discovery— requires

DNA methylation and retinal degenerative diseases: at the crossroad between genes and diet