The LDL receptor in the retina: the missing link in aging, the new target in dietary prevention

Purpose The discovery of the LDL receptor (LDLR) in 1985 by Brown and Goldstein was awarded by a Nobel Prize. The LDLR has initially been identified for its role in mediating the endocytosis of LDL particles in the vascular endothelium. The deposition of lipids, including cholesterol and cholesteryl esters in Bruch’s Membrane in the one hand, and in the vessel intima in the other hand, is one of the common features of age related macular degeneration (AMD) and cardiovascular disease (CVD). Dietary habits with high intakes of omega 3 long chain fatty acids (LCFA) have been associated with AMD prevention. Similar effects have been demonstrated in CVD prevention. The mechanisms behind this association in AMD remain partly unknown. Methods The present paper highlights our recent findings on the pivotal role of LDLR in aging of the retina, and modulation of LDLR expression by dietary omega 3 LCFA. Results In a humanized mouse, we have shown that the lack of LDLR was associated with the presence of the main characteristics of aging of the human retina: fundus autofluorescence, deposition of cholesteryl esters in Bruch’s Membrane, and impairment of the retinal function. We further questioned whether following the dietary guidelines on omega 3 LCFA would modulate gene expression, including LDLR. Expectedly, we found that increasing the intake in omega 3 LCFA and lowering linoleic acid increased LDLR expression and improved the incorporation of omega 3 LCFA. Conclusion Altogether, our data are consistent with the crucial importance of LDLR in the aging process in the retina. We also strongly support the idea that the modulation of LDLR expression is one of the mechanisms of the preventive effects of omega 3 LCFA in AMD.