High-Fat Diet Alters the Retinal Transcriptome in the Absence of Gut Microbiota

Abstract

The relationship between retinal disease, diet, and the gut microbiome has shown increasing importance over recent years. In particular, high-fat diets (HFDs) are associated with development and progression of several retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy. However, the complex, overlapping interactions between diet, gut microbiome, and retinal homeostasis are poorly understood. Using high-throughput RNA-sequencing (RNA-seq) of whole retinas, we compare the retinal transcriptome from germ-free (GF) mice on a regular diet (ND) and HFD to investigate transcriptomic changes without influence of gut microbiome. After correction of raw data, 53 differentially expressed genes (DEGs) were identified, of which 19 were upregulated and 34 were downregulated in GF-HFD mice. Key genes involved in retinal inflammation, angiogenesis, and RPE function were identified. Enrichment analysis revealed that the top 3 biological processes affected were regulation of blood vessel diameter, inflammatory response, and negative regulation of endopeptidase. Molecular functions altered include endopeptidase inhibitor activity, protease binding, and cysteine-type endopeptidase inhibitor activity. Human and mouse pathway analysis revealed that the complement and coagulation cascades are significantly affected by HFD. This study demonstrates novel data that diet can directly modulate the retinal transcriptome independently of the gut microbiome.

Multi-Omics Reveals Inhibitory Effect of Baicalein on Non-Alcoholic Fatty Liver Disease in Mice

“…Recently, gut microbiota is considered to be an important “organ” of the body, which can affect a variety of physiological processes. Dao et al (2021) believed that gut microbiota altered by high-fat diet could modulate the retinal transcriptome, and they proposed a diet–microbiome–retina axis to reveal how diet affects the pathogenesis and severity of retinal diseases. Another report showed that gut microbiota from young donors could reprogram the circadian clock of the lacrimal gland by transcriptomic analysis ( Jiao et al, 2021 ).…”

High-Fat Diet Alters the Retinal Pigment Epithelium and Choroidal Transcriptome in the Absence of Gut Microbiota

“…Gut microbiota may be key mediators of HFDs in retinal disease, whereby HFDs induce gut dysbiosis, increase intestinal permeability, and induce chronic inflammation in AMD models irrespective of total energy intake [31]. We previously studied HFD-induced changes in retinal transcription independent of gut microbiota; however, its impact at the level of the RPE/choroid is unknown [34].…”

“…Within our model, when contrasting these results with previously identified changes in retinal transcription of GF mice, HFDs induced a greater shift in transcription in the RPE/choroid, with little overlap in the genes affected. In fact, the only two overlapping genes were Ms4a6b (membrane spanning 4-domains A6A) and Hbb-bs (hemoglobin subunit beta), both of which were upregulated in the retina and in the RPE/choroid [34]. These transcriptional differences may partly be due to the distinct functions of the retina and RPE/choroid within the visual system, with the RPE/choroid providing barrier protection, nutrients, substrates, and waste clearance for the neural retina [14].…”

The role and mechanisms of gut microbiota in diabetic nephropathy, diabetic retinopathy and cardiovascular diseases

“…Diabetic retinopathy (DR), also called microvascular disease, is a major complication of diabetes causing blindness and vision impairment. About 35% of T2DM patients are affected by DR ( Dao et al, 2021 ). Mechanisms underlying the pathogenesis of DR are multifactorial and intricate.…”