A High-Fat Diet Alters Genes and Susceptibility to Age-Related Macular Degeneration, New Research Shows

High-throughput analysis reveals that retinal genes are influenced by a high-fat diet alone, independent of gut bacteria, in ways that increase susceptibility to macular degeneration.

What: New research in animal models shows that a high-fat diet alone, independent of changes to the gut microbiome, is capable of influencing genes related to the retina in ways that may contribute to age-related macular degeneration (AMD), ie, by turning off some genes and turning on others.

Where: Dao D, et al. “High-Fat Diet Alters the Retinal Transcriptome in the Absence of Gut Microbiota,” Cells, 2021

BrightFocus Connection: This research was funded by a Macular Degeneration Research grant to senior author Dimitra Skondra, MD, PhD, associate professor of Ophthalmology and Visual Science at The University of Chicago and director of the J. Terry Ernest Ocular Imaging Center.

Why It Is Important: Recent studies indicate that age-related macular degeneration (AMD) is exacerbated by a high-fat and/or high-glycemic diet (ie, foods rich in refined sugars and starches) in combination with microorganisms living in the gut (the gut microbiome). However, research into these influences on ocular tissue is in beginning stages, and the interactions between AMD, diet, and the gut microbiome are not well understood, nor are the molecular pathways by which diet affects AMD.

In this first-of-a-kind study, researchers untangled the effects of a high-fat diet and the gut microbiome on the retina by identifying how a high-fat diet in and of itself activates or represses retinal genes and influences diseases like AMD. The research also discovered new genes related to the retina, as well as shed light on the molecular and biochemical processes by which a high-fat diet is involved in AMD.

To isolate the effects of diet from those of the gut microbiome, the researchers fed a high-fat diet to germ-free mice that are devoid of all microorganisms. Their goal was to explore changes in retinal genes induced by diet alone. Using high-throughput RNA sequencing of whole retinas from germ-free mice, the researchers identified genes and pathways involved in retinal inflammation, growth of new blood vessels, and the functioning of the retinal pigment epithelium (RPE), a layer of cells between the retina’s light-sensitive photoreceptors and the blood vessels lying below.

Previous animal studies, including research funded by BrightFocus, have shown that diet can change the makeup of the gut microbiome in ways that raise or lower the risk of AMD; and there is epidemiologic research associating high-fat diet with increased AMD prevalence. This study undertook a novel hypothesis and is among the first to provide early evidence of a direct relationship between a high-fat diet and gene changes related to AMD, separate from the gut microbiome. The results raise the possibility that other interventions involving diet, or treatments directed to gene targets influenced by diet, could be beneficial to treat AMD. More research will be needed to explore treatment and prevention avenues raised by these findings.