A low glycemic diet protects disease-prone Nrf2-deficient mice against age-related macular degeneration

• Published in: Free radical biology & medicine Vol. 150; pp. 75 - 86
• Main Authors: Rowan, Sheldon, Jiang, Shuhong, Chang, Min-Lee, Volkin, Jonathan, Cassalman, Christa, Smith, Kelsey M., Streeter, Matthew D., Spiegel, David A., Moreira-Neto, Carlos, Rabbani, Naila, Thornalley, Paul J., Smith, Donald E., Waheed, Nadia K., Taylor, Allen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2020
• Subjects: Advanced glycation end-product; Animals; Antioxidant; Diet; Geographic atrophy; Glycation End Products, Advanced; Glycemic index; Macular Degeneration - genetics; Macular Degeneration - prevention & control; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2 - genetics; Retinal Pigment Epithelium; Retinal pigmented epithelium; Geographic atrophy; Advanced glycation end-product; Glycemic index; Retinal pigmented epithelium; Antioxidant
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2020.02.010

Age-related macular degeneration (AMD) is a major blinding disease, affecting over 14% of the elderly. Risk for AMD is related to age, diet, environment, and genetics. Dietary modulation of AMD risk is a promising treatment modality, but requires appropriate animal models to demonstrate advantages of diet. Mice lacking the antioxidant transcription factor Nrf2 (Nfe2l2) develop age-related retinopathy relevant to human AMD. Here we evaluated the effect of consuming high glycemic (HG) or low glycemic (LG) diets until 18-months of age on development of features relevant to AMD in Nrf2-null mice. Nrf2-null mice that consumed HG diets developed atrophic AMD, characterized by photoreceptor degeneration, retinal pigment epithelium (RPE) atrophy and pigmentary abnormalities, basal laminar deposits, and loss of the choriocapillaris. In contrast, Nrf2-null-mice that consumed LG diets did not develop retinal disease phenotypes. Consumption of HG diets was associated with accumulation of advanced glycation end-products in the RPE and systemically, whereas consumption of the LG diet was associated with increased levels of anti-glycative and anti-oxidative detoxification machinery. Together our data indicate that the Nrf2-null HG mouse is a good model for atrophic AMD studies and that the LG diet can activate protective pathways to prevent AMD, even in a genetically predisposed animal. [Display omitted] •Nrf2-null mice fed high glycemic diets develop features relevant to dry AMD.•AMD-relevant features include degeneration of RPE, photoreceptors, and choriocapillaris.•Nrf2-null mice fed low glycemic diets do not develop AMD-releveant features.•Advanced glycation end-products are increased in the RPE by high glycemic diet.•Low glycemic diet-fed mice have increased levels of antioxidant enzymes in the RPE.