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Journal of Diabetes and Clinical Research

ISSN: 2689-2839

Original Research Open Access
Volume 7 | Issue 1 | DOI: https://doi.org/10.33696/diabetes.6.070

Inhibition of Sortilin Improves Retinal Function in Diabetic Mice Through Decreased Inflammatory Mediators

Li Liu1, Youde Jiang1, Robert Wright1, Mohamed Al-Shabrawey2,3, Jena J. Steinle1,*
  • 1Department of Ophthalmology, Visual and Anatomical Sciences, Center for Molecular and Medical Genetics, Wayne State University School of Medicine, Detroit, MI, USA
  • 2Eye Research Center and Institute, Oakland University William Beaumont School of Medicine (OUWB-SOM), Oakland University, Oakland, MI 48309, USA
  • 3Department of Foundational Medical Studies, OUWB-SOM, Oakland University, USA
+ Affiliations - Affiliations

Corresponding Author

Jena J Steinle, jsteinle@med.wayne.edu

Received Date: July 03, 2025

Accepted Date: September 10, 2025

Citation:

Liu L, Jiang Y, Wright R, Al-Shabrawey M, Steinle JJ. Inhibition of Sortilin Improves Retinal Function in Diabetic Mice Through Decreased Inflammatory Mediators. J Diabetes Clin Res. 2025;7(1):44–51.


Copyright: © 2025 Liu L, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Inflammation is a key factor in retinal damage in response to diabetes. Sortilin represents a new regulator of retinal inflammation. Sortilin is involved in over 50 different signaling cascades. To investigate sortilin in the diabetic retina, we first measured protein levels in retinal lysates from diabetic humans and diabetic mice. We then inhibited sortilin using a small molecule inhibitor, AF38469, and evaluated retinal function using electroretinogram (ERG) and fluorescein angiography. We also measured key inflammatory and autophagic proteins. Data showed that sortilin levels were significantly increased in retinal lysates from diabetic patients and diabetic mice. Treatment of mice with AF38469 in their drinking water restored ERG and angiography to normal levels in diabetic mice. We found that AF38469 reduced high mobility group box 1 (HMGB1) and interleukin-1beta (IL-1β) levels. We also found that inhibiting sortilin led to reduced LAMP2 levels in diabetic mice. In conclusion, our data suggest that inhibition of sortilin may offer a new pathway to protect the diabetic retina.

Keywords

Diabetic Retinopathy, Sortilin, Retina, Therapeutics

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