Natural History of Age-Related Retinal Lesions That Precede AMD in Mice Fed High or Low Glycemic Index Diets

Weikel, Karen A.; Fitzgerald, Paul G.; Shang, Fu; Caceres, Maria Andrea; Bian, Qingning; Handa, James T.; Stitt, Alan W.; Taylor, Allen

doi:10.1167/iovs.11-8545

Cited by 48 publications

(46 citation statements)

References 135 publications

(59 reference statements)

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“…To evaluate the effects of dietary glycemia on development of age-related eye disease, we fed middle-aged (12-mo-old) mice HG and LG diets until they reached old age (24 mo). The HG and LG diets differed only in the ratio of amylose/amylopectin starches and were isocaloric (Methods) (10,19). Exchanging amylose for amylopectin increases the GI of the diet.…”

Section: Resultsmentioning

confidence: 99%

“…The full dietary regimen, including numbers of animals, is summarized in Fig. S1 A and B. Diets contained identical macronutrient compositions with the exception that the HG starch was composed of 100% amylopectin (Amioca starch; Ingredion, Inc.), whereas the LG starch was composed of 70% amylose/30% amylopectin (HYLON VII starch; Ingredion Incorporated) (10). All diets were formulated by Bio-Serv.…”

Section: Methodsmentioning

confidence: 99%

“…Increased levels of advanced glycation end products (AGEs), i.e., covalent posttranslational oxidative and nonoxidative modifications of proteins by sugar-derived metabolites, were observed in the mice fed a high-glycemia (HG) diet (hereafter, "HG mice") (10,11). AGEs are cytotoxic (12), and this cytotoxicity is corroborated by the accumulation of AGEs in AMD.…”

Section: Significancementioning

confidence: 99%

“…Despite lacking a macula, the mouse retina shows many AMDf and has been useful for relating risk factors for AMD, including cigarette smoking, diet, and inflammation (10,(14)(15)(16)(17)(18). Here we tested the hypothesis that changing from an HG to an LG diet even during maturity can delay or arrest AMDf.…”

Section: Significancementioning

confidence: 99%

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Involvement of a gut–retina axis in protection against dietary glycemia-induced age-related macular degeneration

Rowan

Jiang

Korem

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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190

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Age-related macular degeneration (AMD) is the major cause of blindness in developed nations. AMD is characterized by retinal pigmented epithelial (RPE) cell dysfunction and loss of photoreceptor cells. Epidemiologic studies indicate important contributions of dietary patterns to the risk for AMD, but the mechanisms relating diet to disease remain unclear. Here we investigate the effect on AMD of isocaloric diets that differ only in the type of dietary carbohydrate in a wild-type aged-mouse model. The consumption of a high-glycemia (HG) diet resulted in many AMD features (AMDf), including RPE hypopigmentation and atrophy, lipofuscin accumulation, and photoreceptor degeneration, whereas consumption of the lower-glycemia (LG) diet did not. Critically, switching from the HG to the LG diet late in life arrested or reversed AMDf.LG diets limited the accumulation of advanced glycation end products, long-chain polyunsaturated lipids, and their peroxidation end-products and increased C3-carnitine in retina, plasma, or urine. Untargeted metabolomics revealed microbial cometabolites, particularly serotonin, as protective against AMDf. Gut microbiota were responsive to diet, and we identified microbiota in the Clostridiales order as being associated with AMDf and the HG diet, whereas protection from AMDf was associated with the Bacteroidales order and the LG diet. Network analysis revealed a nexus of metabolites and microbiota that appear to act within a gut-retina axis to protect against diet-and age-induced AMDf. The findings indicate a functional interaction between dietary carbohydrates, the metabolome, including microbial cometabolites, and AMDf. Our studies suggest a simple dietary intervention that may be useful in patients to arrest AMD.age-related macular degeneration | glycemic index | advanced glycation end-product | gut microbiome | metabolomics A ge-related macular degeneration (AMD) is the leading cause of irremediable blindness in the industrialized world, with 200 million cases projected by 2020, at a cost of $300 billion (1, 2). Dry AMD accounts for the great majority of cases and is associated with photoreceptor cell loss, often preceded by compromise to the retina pigment epithelium (RPE) cells that nourish and remove waste from the photoreceptors. The etiology of AMD remains an enigma but is clearly multifactorial. Stresses associated with AMD include environment, age, and genetics (3). Frustratingly, there are no early biomarkers to anticipate AMD, and there are no therapies or cure.Recently, we and others observed in epidemiologic studies that, in addition to micronutrients (4-6), macronutrient quality [e.g., consuming a diet with a high glycemic index (GI)] is a significant risk factor for AMD onset and/or progress in nondiabetic humans (7)(8)(9). The GI appears to be an attractive dietary intervention target, because simple replacement of small amounts of high-index foods (such as white bread) with lower-index foods (such as wholegrain bread) can significantly reduce glycemic peaks without requiring ...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

Section: Significancementioning

confidence: 99%

See 2 more Smart Citations

Involvement of a gut–retina axis in protection against dietary glycemia-induced age-related macular degeneration

Rowan

Jiang

Korem

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

190

192

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“…With age, there is a change in the pigmentation pattern, reduction of melanosomes, and cell density of RPE and an increase in the number of lipofuscin granules. There are also reports on accumulation of advanced glycation end products in RPE and Bruch's membrane that might contribute toward oxidative stress in the ECM environment (16)(17)(18). Hence, in atrophic AMD, there is an increase in oxidative stress due to compromised protective mechanisms of RPE.…”

Section: Introductionmentioning

confidence: 99%

Novel Endogenous Glycan Therapy for Retinal Diseases: Safety, In Vitro Stability, Ocular Pharmacokinetic Modeling, and Biodistribution

Swaminathan

Palamoor

et al. 2014

AAPS J

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Abstract. Asialo, tri-antennary oligosaccharide (NA3 glycan) is an endogenous compound, which supports proper folding of outer segment membranes, promotes normal ultrastructure, and maintains protein expression patterns of photoreceptors and Müller cells in the absence of retinal pigment epithelium support. It is a potential new therapeutic for atrophic age-related macular degeneration (AMD) and other retinal degenerative disorders. Herein, we evaluate the safety, in vitro stability, ocular pharmacokinetics and biodistribution of NA3. NA3 was injected into the vitreous of New Zealand white rabbits at two concentrations viz. 1 nM (minimum effective concentration (MEC)) and 100 nM (100XMEC) at three time points. Safety was evaluated using routine clinical and laboratory tests. Ocular pharmacokinetics and biodistribution of [ 3 H]NA3 were estimated using scintillation counting in various parts of the eye, multiple peripheral organs, and plasma. Pharmacokinetic parameters were estimated by non-compartmental modeling. A 2-aminobenzamide labeling and hydrophilic interaction liquid interaction chromatography were used to assess plasma and vitreous stability. NA3 was well tolerated by the eye. The concentration of NA3 in eye tissues was in the order: vitreous>retina>sclera/choroid> aqueous humor>cornea>lens. Area under the curve (0 to infinity) (AUC∞) was the highest in the vitreous thereby providing a positive concentration gradient for NA3 to reach the retina. Half-lives in critical eye tissues ranged between 40 and 60 h. NA3 concentrations were negligible in peripheral organs. Radioactivity from [ 3 H]NA3 was excreted via urine and feces. NA3 was stable at 37°C in vitreous over a minimum of 6 days, while it degraded rapidly in plasma. Collectively, these results document that NA3 shows a good safety profile and favorable ocular pharmacokinetics.

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Animal Models of Diseases of the Retinal Pigment Epithelium

Fletcher

Greferath

Guennel

et al. 2020

Retinal Pigment Epithelium in Health and Disease

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Natural History of Age-Related Retinal Lesions That Precede AMD in Mice Fed High or Low Glycemic Index Diets

Cited by 48 publications

References 135 publications

Involvement of a gut–retina axis in protection against dietary glycemia-induced age-related macular degeneration

Involvement of a gut–retina axis in protection against dietary glycemia-induced age-related macular degeneration

Novel Endogenous Glycan Therapy for Retinal Diseases: Safety, In Vitro Stability, Ocular Pharmacokinetic Modeling, and Biodistribution

Animal Models of Diseases of the Retinal Pigment Epithelium

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