Research Paper Volume 13, Issue 1 pp 973—990
Tandem mass tag-based proteomic analysis reveals cathepsin-mediated anti-autophagic and pro-apoptotic effects under proliferative diabetic retinopathy
- 1 Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
- 2 Hetian District People's Hospital, Xinjiang, China
Received: March 25, 2020 Accepted: October 8, 2020 Published: December 3, 2020https://doi.org/10.18632/aging.202217
How to Cite
Copyright: © 2020 Niu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Proliferative diabetic retinopathy (PDR) is a severe complication of diabetes and can cause blindness. However, the available therapeutic modalities to PDR have unsatisfactory efficacies and incur adverse effects, which is due to the paucity in the understanding of pathogenic mechanisms responsible for the disease. In this study, tandem mass tag labeling technology combined with liquid chromatography and tandem mass spectrometry were utilized to identify differentially expressed proteins in vitreous humor of patients with rhegmatogenous retinal detachment and PDR. The data are available via ProteomeXchange with identifier PXD021788. Afterwards, the downregulated protein expression of Cathepsin B, D, and L was verified in vitreous and serum of another cohort. The gene expression profiling of the 3 cathepsins was confirmed in blood cells of an extra cohort. Furthermore, in high glucose (HG)-treated retinal vascular endothelial cell cultures recapitulating the cathepsin expression patterns, Cathepsin B or D downregulation mediated the HG-induced anti-autophagic and pro-apoptotic effects, thereby may contribute to vascular lesions under hyperglycemia. This study demonstrates previously undescribed expression patterns of cathepsins, reveals a novel cathepsin-involved pathogenic mechanism under PDR, and sheds light on potential therapeutic targets to this debilitating retinal disease.