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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Translational Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1490443

Supplementation of dipeptide alanine-glutamine ameliorates retinal neurodegeneration in an STZ-induced rat model

Provisionally accepted
Qian Chen Qian Chen 1,2*Yuhan Zhang Yuhan Zhang 1,2Mingyan Wei Mingyan Wei 1,2Xin Wang Xin Wang 1,2Yuan Xu Yuan Xu 1,2Rongrong zong Rongrong zong 1,2Xiang Lin Xiang Lin 3ShiYing Li ShiYing Li 4Wensheng Chen Wensheng Chen 1,2Zuguo Liu Zuguo Liu 1,2
  • 1 Eye Institute, Xiamen University, Xiamen, China
  • 2 Eye Center, Xiamen University, Xiamen, Fujian Province, China
  • 3 Xiang'an Hospital, Xiamen University, Xiamen, Fujian Province, China
  • 4 First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, China

The final, formatted version of the article will be published soon.

    Diabetic retinopathy (DR) is a common complication of diabetes. Retinal neuronal degeneration is an early event in DR, indicated by the declined electroretinogram (ERG). Dipeptide alanine-glutamine (Ala-Gln) is widely used as a nutritional supplement in the clinic and has anti-inflammatory effects on the gastrointestinal system. Studies also reported that glutamine has beneficial effects on diabetes. This study aimed to investigate the possible therapeutic effects of Ala-Gln in diabetic retinal neurodegeneration and to delineate its mechanism of action. The Streptozotocin (STZ)-induced rat model was used as a DR model. ERG was used to measure the neuronal function of the retina.Western blot analysis was performed to test the expression of proteins.Immunofluorescence staining was used for detection and localization of proteins. In diabetic rats, the amplitudes of ERG were declined, while Ala-Gln restored the declined ERG. Retinal levels of inflammatory factors were significantly decreased in Ala-Gln-treated diabetic rats. Ala-Gln mitigated the declined levels of glutamine synthetase and ameliorated the upregulated levels of glial fibrillary acidic protein (GFAP) in diabetic retinas. Moreover, Ala-Gln upregulated the glycolytic enzymes pyruvate kinase isozymes 2 (PKM2), lactate dehydrogenase A (LDHA) and LDHB and stimulated the mTOR signaling pathway in diabetic retinas. The mitochondrial function was improved after the treatment of Ala-Gln in diabetic retinas. In summary, Ala-Gln ameliorates retinal neurodegeneration by reducing inflammation and enhancing glucose metabolism and mitochondrial function in DR. Therefore, manipulation of metabolism by Ala-Gln may be a novel therapeutic avenue for retinal neurodegeneration in DR.

    Keywords: Diabetic Retinopathy, Alanine-glutamine, retinal neurodegeneration, glucose metabolism, mTOR

    Received: 03 Sep 2024; Accepted: 06 Nov 2024.

    Copyright: © 2024 Chen, Zhang, Wei, Wang, Xu, zong, Lin, Li, Chen and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Qian Chen, Eye Institute, Xiamen University, Xiamen, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.