Impacts of high fat diet on ocular outcomes in rodent models of visual disease

• Type of Material: Article
• Authors: Danielle A Clarkson-Townsend, Emory University; Amber J Douglass, Atlanta VA Healthcare System; Anayesha Singh, Atlanta VA Healthcare System; Rachael Allen, Emory University; Ivie N Uwaifo, Atlanta VA Healthcare System; Machelle Pardue, Emory University
• Language: English
• Date: 2021-01-16
• Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Published by Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.exer.2021.108440
• Title of Journal or Parent Work: EXPERIMENTAL EYE RESEARCH
• Volume: 204
• Start Page: 108440
• End Page: 108440
• Grant/Funding Information: This work was supported by funding from the National Institutes of Health (NIH-NICHD F31 HD097918 [to DACT], NIH-NIEHS T32 ES012870 [to DACT], NIH-NEI Core Grant P30EY006360) and the Department of Veterans Affairs (Rehabilitation Research and Development Senior Research Career Scientist Award RX003134 [to MTP] and Career Development Award CDA-2 RX002928 [to RSA]). The study sponsors did not have any role in the study design, collection, analysis, interpretation of the data, writing of the report, or the decision to submit the paper for publication.
• Keywords: High fat diet; Diabetes; Retina; Diet-induced obesity; MACULAR DEGENERATION; HFD; Age-related macular degeneration; Life Sciences & Biomedicine; INSULIN-RESISTANCE; DIABETIC-RETINOPATHY; Ophthalmology; BRUCHS MEMBRANE; SUB-RPE DEPOSITS; Diabetic retinopathy; Science & Technology; Vision; PERIPHERAL NEUROPATHY; INDUCED OBESITY; RETINAL-PIGMENT EPITHELIUM; ANIMAL-MODELS; BASAL LAMINAR DEPOSIT

Abstract

High fat diets (HFD) have been utilized in rodent models of visual disease for over 50 years to model the effects of lipids, metabolic dysfunction, and diet-induced obesity on vision and ocular health. HFD treatment can recapitulate the pathologies of some of the leading causes of blindness, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) in rodent models of visual disease. However, there are many important factors to consider when using and interpreting these models. To synthesize our current understanding of the importance of lipid signaling, metabolism, and inflammation in HFD-driven visual disease processes, we systematically review the use of HFD in mouse and rat models of visual disease. The resulting literature is grouped into three clusters: models that solely focus on HFD treatment, models of diabetes that utilize both HFD and streptozotocin (STZ), and models of AMD that utilize both HFD and genetic models and/or other exposures. Our findings show that HFD profoundly affects vision, retinal function, many different ocular tissues, and multiple cell types through a variety of mechanisms. We delineate how HFD affects the cornea, lens, uvea, vitreous humor, retina, retinal pigmented epithelium (RPE), and Bruch's membrane (BM). Furthermore, we highlight how HFD impairs several retinal cell types, including glia (microglia), retinal ganglion cells, bipolar cells, photoreceptors, and vascular support cells (endothelial cells and pericytes). However, there are a number of gaps, limitations, and biases in the current literature. We highlight these gaps and discuss experimental design to help guide future studies. Very little is known about how HFD impacts the lens, ciliary bodies, and specific neuronal populations, such as rods, cones, bipolar cells, amacrine cells, and retinal ganglion cells. Additionally, sex bias is an important limitation in the current literature, with few HFD studies utilizing female rodents. Future studies should use ingredient-matched control diets (IMCD), include both sexes in experiments to evaluate sex-specific outcomes, conduct longitudinal metabolic and visual measurements, and capture acute outcomes. In conclusion, HFD is a systemic exposure with profound systemic effects, and rodent models are invaluable in understanding the impacts on visual and ocular disease.