2. Academic Validation
  3. Drp1-dependent mitochondrial fragmentation mediates photoreceptor abnormalities in type 1 diabetic retina

Drp1-dependent mitochondrial fragmentation mediates photoreceptor abnormalities in type 1 diabetic retina

  • Exp Eye Res. 2024 Mar 9:109860. doi: 10.1016/j.exer.2024.109860.
Shuyu Tang 1,  Mengling Huang 1,  Ruixuan Wang 2,  Ming Li 3,  Ning Dong 1,  Ronghan Wu 4,  Zailong Chi 5,  Ling Gao 6
Affiliations

Affiliations

  • 1 Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, China.
  • 2 Bourns Engineering, The University of California, Riverside, Riverside, CA, 92521, United States.
  • 3 Department of Immunology, College of Basic Medical Immunology, Central South University, Changsha, China.
  • 4 State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital of Wenzhou Medical University, Wenzhou, China; National Clinical Research Center for Ocular Diseases, Eye Hospital of Wenzhou Medical University, Wenzhou, China.
  • 5 State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital of Wenzhou Medical University, Wenzhou, China; National Clinical Research Center for Ocular Diseases, Eye Hospital of Wenzhou Medical University, Wenzhou, China. Electronic address: zailong.chi@eye.ac.cn.
  • 6 Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, China; State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital of Wenzhou Medical University, Wenzhou, China; National Clinical Research Center for Ocular Diseases, Eye Hospital of Wenzhou Medical University, Wenzhou, China. Electronic address: gaoling6287@csu.edu.cn.
PMID: 38467174 DOI: 10.1016/j.exer.2024.109860
Abstract

Recent studies have highlighted that retinal neurodegeneration precedes microvascular changes in diabetic retinopathy (DR), but the specific mechanisms remain unclear. Given the pivotal role of dysfunctional mitochondria and oxidative stress in early DR, our objective was to observe mitochondria-related alterations in the neural retina of type one diabetic mellitus mice with no evidence of DR (T1DM-NDR). We aimed to identify the key mitochondrial-related proteins contributing to mitochondrial injury. Our study revealed that T1DM-NDR mice exhibited outer retina thinning, including the ellipsoid zone, inner segment, and outer segment. Additionally, there was an impaired amplitude of the b-wave in electroretinogram (ERG) and a disorganized arrangement of the photoreceptor layer. In both the retina of DM mice and high glucose (HG)-treated 661w cells, mitochondria appeared swollen and fragmented, with disrupted cristae, disorganized or shortened branches in the mitochondrial network, and decreased mitochondrial membrane potential. Among the mitochondrial-related proteins, dynamin-related protein 1 (Drp1) was upregulated, and the ratio of phosphorylated Drp1 protein at serine 616 (S616) and serine 637 (S637) sites significantly increased in the retina of DM mice. The administration of Mdivi-1 ameliorated high-glucose-induced dysfunctional mitochondria, thereby protecting T1DM-NDR mice retina from morphological and functional injuries. Our findings suggest that hyperglycemia promotes Drp1-mediated mitochondrial dysfunction, which may be a significant factor in the development of DR. The inhibition of high-glucose-induced mitochondrial fission emerges as a potential and innovative intervention strategy for preventing DR.

Keywords

Diabetic retinopathy; Drp1; Mitochondria; Photoreceptor; T1DM.

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