MicroRNA‐150 and its target ETS‐domain transcription factor 1 contribute to inflammation in diabetic photoreceptors

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.

Fatty Acid-Binding Protein 4 in Patients with and without Diabetic Retinopathy

“…The number of T2DM patients is expected to increase to 642 million by 2040 [ 1 ]. According to conservative estimates, approximately 60% of T2DM patients eventually develop DR in their lifetime [ 2 ]. A person with diabetes has a 25-fold increased risk of blindness compared to those without diabetes [ 3 ].…”