Dual roles of polyunsaturated fatty acids in retinal physiology and pathophysiology associated with retinal degeneration

Abstract

Retinas are highly enriched with long-chain polyunsaturated fatty acids (PUFAs). The reduction of docosahexenoic acid in the photoreceptor outer segment membrane leads to a reduction in the electroretinographic response, suggesting crucial roles for PUFAs in normal retinal physiology. Epidemiological studies suggest a correlation between environmental light exposure and the development/progression of human retinal degenerations such as age-related macular degeneration and retinitis pigmentosa. The double bonds in PUFAs could be target substrates to propagate photooxidative stress in photoreceptors. Light exposure to animals results in selective losses of photoreceptor and retinal pigment epithelial cells and post-translational modifications of retinal proteins by 4-hydroxynonenal and 4-hydroxyhexenal. These end products of nonezymatic oxidation of n-6 and n-3 PUFAs, respectively, are likely to be involved in the light-induced retinal degeneration. Low levels of 4-HNE generated by low levels of environmental light exposure upregulate endogenous redox molecules such as thioreodoxin and thioreodoxin reductase via the nuclearfactor E2-related factor 2/antioxidant-responsive element pathway in the retina, and confer retinal neuroprotection. This paper highlights the dual roles of retinal PUFAs in cellular physiology and pathology.