Abstract
Presentation Description :
A plethora of literature attests to the advantages of consuming lower glycemia diets (LG) with respect to CVD, type 2 diabetes and, more recently, age related macular degeneration (AMD)1. Intervention trials are required to prove the associations and to design new pharmacologic approaches for visual health.
In order to justify them, we studied diet-AMD relationships in two models2-4. As in humans, LG diets fed to mice protect against many features of AMD. Impressively, this benefit was observed even in Nrf2-/- mice, that are compromised with regard to antioxidant defenses. Specific metabolites that are associated with AMD features include pentosidine, glucosepane, fatty acids and microbial cometabolites such as serotonin. Mechanistic investigations into protein quality control pathways, including the ubiquitin and autophagic lysosomal pathways, indicate that both are involved in removal of glycatively modified proteins. Glycative stress compromises autophagosome assembly and proteolysis by autophagic and ubiquitin proteolytic pathways. P62 is a chaperone that chaperones glycated cargo to the autophagic pathways. We conclude that consuming LG diets and lower glycative stress provide multiple health benefits including enhanced protein quality control capacities, more beneficial microbiome composition, retention of normal lipid metabolism.
1. Chiu C-J, Liu, S., Willett, W. C., Wolever, T.M.S., Brand-Miller, J. C. Barclay, A. C., A. Taylor. Informing food choices and health outcomes by use of the dietary glycemic index Nutrition Reviews 2011;69:231-42.
2. Uchiki T, Weikel KA, Jiao W, et al. Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in non diabetics). Aging Cell 2012;11:1-13.
3. Weikel KA, Fitzgerald P, Shang F, et al. Natural history of age-related retinal lesions that precede AMD in mice fed high or low glycemic index diets. Invest Ophthalmol Vis Sci 2012;53:622-32.
4. Rowan S, Jiang S, Korem T, et al. Involvement of a gut-retina axis in protection against dietary glycemia-induced age-related macular degeneration. Proc Natl Acad Sci USA 2017;114:E4472-E81.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.