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Abstract
Introduction Diabetic retinopathy (DR) is the leading cause of blindness among the working population in the USA. Current therapies, including anti-vascular endothelial growth factor treatments, cannot completely reverse the visual defects induced by DR. MicroRNA-150 (miR-150) is a regulator that suppresses inflammation and pathological angiogenesis. In patients with diabetes, miR-150 is downregulated. As chronic inflammation is a major contributor to the pathogenesis of DR, whether diabetes-associated decrease of miR-150 is merely associated with the disease progression or decreased miR-150 causes retinal inflammation and pathological angiogenesis is still unknown.
Research design and methods We used high-fat diet (HFD)-induced type 2 diabetes (T2D) in wild type (WT) and miR-150 knockout (miR-150-/-) mice for this study and compared retinal function and microvasculature morphology.
Results We found that WT mice fed with an HFD for only 1 month had a significant decrease of miR-150 in the blood and retina, and retinal light sensitivity also decreased. The miR-150-/- mice on the HFD developed diabetes similar to that of the WT. At 7–8 months old, miR-150-/- mice under normal diet had increased degeneration of retinal capillaries compared with WT mice, indicating that miR-150 is important in maintaining the structural integrity of retinal microvasculature. Deletion of miR-150 worsened HFD-induced retinal dysfunction as early as 1 month after the diet regimen, and it exacerbated HFD-induced T2DR by further increasing retinal inflammation and microvascular degeneration.
Conclusion These data suggest that decreased miR-150 caused by obesity or diabetic insults is not merely correlated to the disease progression, but it contributes to the retinal dysfunction and inflammation, as well as the development of DR.
- blindness
- diabetes mellitus
- Type 2
- diabetic retinopathy
- obesity
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Footnotes
Presented at Parts of this study were presented in abstract form at the Society for Neuroscience 2019 Annual Conference, Chicago, Illinois, USA, 19–23 October 2019. Yu, F., Chapman, S., Ko, M.L., and Ko, G. Y.-P. The role of microRNA-150 in the pathogenesis of diabetic retinopathy. Society for Neuroscience, 575.02, 2019.
Contributors FY performed the experiments, analyzed the data, assisted in manuscript preparation, and was involved in writing of the manuscript. FY had full access to all the data in the study. SC and DLP assisted in data analyses. MLK and BZ assisted in manuscript preparation and editing. GYPK designed the study, provided experimental oversight, assisted in data analysis, and wrote the manuscript. GYPK is the guarantor of this work, and as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Funding This work was in part supported by a graduate research award from the College of Veterinary Medicine and Biomedical Sciences at Texas A&M University to FY and a philanthropic gift fund for DR and vision research to GYPK.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request. All data relevant to the study are included in the article. FY is the first author of this work, and GYPK is the guarantor of this work. As such, FY and GYPK have full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All data relevant to the study are included in the article, and data are available on reasonable request.