A dark side to omega-3 fatty acids

Abstract

The molecule 19,20-dihydroxydocosapentaenoic acid, formed by the metabolism of a fatty acid involved in normal brain function, promotes the development of a diabetes-associated form of blindness in a mouse model.

Figure 1 |. Abnormal lipid dynamics in diabetic retinopathy.

Hu et al. have shown that increases in levels of the molecule 19,20-DHDP promote the development and progression of a form of visual impairment called diabetic retinopathy in mice. a, Under normal conditions, the endothelial cells that line blood vessels in the retina are connected to one another and to supporting cells called pericytes through adhesion molecules known as cadherins in cell membranes. These connections rely on associations between the cadherins and the protein presenilin 1, which are, in turn, facilitated by clustering of cholesterol on ‘lipid rafts’. b, The authors show that, during the early stages of diabetic retinopathy, increases in 19,20-DHDP in cell membranes (not shown) alter the distribution of presenilin 1, perhaps by disrupting the distribution of cholesterol molecules. Presenilin 1, no longer restrained to lipid rafts, does not associate with cadherins, leading to cadherin internalization in vesicles. This destabilizes cell cell contacts, resulting in pericyte ‘dropout’ from around vessels, and vascular leakage.