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

ABSTRACT: 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.

SUBMITTER: Rowan S

PROVIDER: S-EPMC7747150 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

Rowan Sheldon S Jiang Shuhong S Chang Min-Lee ML Volkin Jonathan J Cassalman Christa C Smith Kelsey M KM Streeter Matthew D MD Spiegel David A DA Moreira-Neto Carlos C Rabbani Naila N Thornalley Paul J PJ Smith Donald E DE Waheed Nadia K NK Taylor Allen A

Free radical biology & medicine 20200214

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 glyce ...[more]

PMID: 32068111

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Project description:PurposeUnhealthy lifestyles have been associated with increased odds for age-related macular degeneration (AMD). Whether this association is modified by genetic risk for AMD is unknown and was investigated.DesignInteractions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalence of AMD, assessed 6 years later.ParticipantsWomen 50 to 79 years of age in the Carotenoids in Age-Related Eye Disease Study with exposure and AMD data (n=1663).MethodsHealthy lifestyle scores (0-6 points) were assigned based on Healthy Eating Index scores, physical activity (metabolic equivalent of task hours/week), and smoking pack years assessed in 1994 and 1998. Genetic risk was based on Y402H in complement factor H (CFH) and A69S in age-related maculopathy susceptibility locus 2 (ARMS2). Additive and multiplicative interactions in odds ratios were assessed using the synergy index and a multiplicative interaction term, respectively.Main outcome measuresAMD presence and severity were assessed from grading of stereoscopic fundus photographs taken in 2001-2004. AMD was present in 337 women, 91% of whom had early AMD.ResultsThe odds of AMD were 3.3 times greater (95% confidence interval [CI], 1.8-6.1) in women with both low healthy lifestyle score (0-2) and high-risk CFH genotype (CC), relative to those who had low genetic risk (TT) and high healthy lifestyle scores (4-6). There were no significant additive (synergy index [SI], 1.08; 95% CI, 0.70-1.67) or multiplicative (Pinteraction=0.94) interactions in the full sample. However, when limiting the sample to women with stable diets before AMD assessment (n=728) the odds for AMD associated with low healthy lifestyle scores and high-risk CFH genotype were strengthened (odds ratio, 4.6; 95% CI, 1.8-11.6) and the synergy index was significant (SI, 1.34; 95% CI, 1.05-1.70). Adjusting for dietary lutein and zeaxanthin attenuated, and therefore partially explained, the joint association. There were no significant additive or multiplicative interactions for ARMS2 and lifestyle score.ConclusionsHaving unhealthy lifestyles and 2 CFH risk alleles increased AMD risk (primarily in the early stages), in an or additive or greater (synergistic) manner. However, unhealthy lifestyles increased AMD risk regardless of AMD risk genotype.

Dataset Information

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

Publications

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

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