Affiliation: | 1. Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Methodology (equal), Validation (equal), Writing - original draft (equal);2. Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA Department of Biology, Division of Natural and Physical Sciences, Blinn College, Bryan, Texas, USA;3. Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA |
Abstract: | Obesity-associated type 2 diabetes (T2D) is on the rise in the United States due to the obesity epidemic, and 60% of T2D patients develop diabetic retinopathy (DR) in their lifetime. Chronic inflammation is a hallmark of obesity and T2D and a well-accepted major contributor to DR, and retinal photoreceptors are a major source of intraocular inflammation and directly contribute to vascular abnormalities in diabetes. However, how diabetic insults cause photoreceptor inflammation is not well known. In this study, we used a high-fat diet (HFD)-induced T2D mouse model and cultured photoreceptors treated with palmitic acid (PA) to decipher major players that mediate high-fat-induced photoreceptor inflammation. We found that PA-elicited microRNA-150 (miR-150) decreases with a consistent upregulation of ETS-domain transcription factor 1 (Elk1), a downstream target of miR-150, in PA-elicited photoreceptor inflammation. We compared wild-type (WT) and miR-150 null (miR-150−/−) mice fed with an HFD and found that deletion of miR-150 exacerbated HFD-induced photoreceptor inflammation in conjunction with upregulated ELK1. We further delineated the critical cellular localization of phosphorylated ELK1 at serine 383 (pELK1S383) and found that decreased miR-150 exacerbated the T2D-induced inflammation in photoreceptors by upregulating ELK1 and pELK1S383, and knockdown of ELK1 alleviated PA-elicited photoreceptor inflammation. |