Autophagy and senescence of rat retinal precursor cells under high glucose

Hanhan Peng; Wentao Han; Benteng Ma; Shirui Dai; Jianfeng Long; Shu Zhou; Haoyu Li; Baihua Chen

doi:10.3389/fendo.2022.1047642

Autophagy and senescence of rat retinal precursor cells under high glucose

Front Endocrinol (Lausanne). 2023 Jan 4:13:1047642. doi: 10.3389/fendo.2022.1047642. eCollection 2022.

Authors

Hanhan Peng^{1

2}, Wentao Han^{1

2}, Benteng Ma^{1

2}, Shirui Dai^{1

2}, Jianfeng Long^{1

2}, Shu Zhou^{1

2}, Haoyu Li^{1

2}, Baihua Chen^{1

2}

Affiliations

¹ Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, China.
² Hunan Clinical Research Centre of Ophthalmic Disease, Changsha, China.

Abstract

Backgrounds: Diabetic retinopathy (DR) is a common diabetic ocular disease characterized by retinal ganglion cell (RGC) changes. An abnormal environment, hyperglycemia, may progressively alter the structure and function of RGCs, which is a primary pathological feature of retinal neurodegeneration in DR. Accumulated studies confirmed autophagy and senescence play a vital role in DR; however, the underlying mechanisms need to be clarified.

Methods: This study included the microarray expression profiling dataset GSE60436 from Gene Expression Omnibus (GEO) to conduct the bioinformatics analysis. The R software was used to identify autophagy-related genes (ARGs) that were differentially expressed in fibrovascular membranes (FVMs) and normal retinas. Co-expression and tissue-specific expression were elicited for the filtered genes. The genes were then analyzed by ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Set Enrichment Analysis (GSEA). R28 cells were cultured with high glucose, detected by reverse transcription-quantitative (RT-qPCR) and stained by apoptosis kit.

Results: In the retina, 31 differentially expressed ARGs (24 up-regulated genes) were discovered and enriched. The enrichment results revealed that differentially expressed ARGs were significantly enriched in autophagy, apoptosis, aging, and neural function. Four hub genes (i.e., TP53, CASP1, CCL2, and CASP1) were significantly up-regulated. Upregulation of cellular autophagy and apoptosis level was detected in the hyperglycemia model in vitro.

Conclusions: Our results provide evidence for the autophagy and cellular senescence mechanisms involved in retinal hyperglycemia injury, and the protective function of autophagy is limited. Further study may favour understanding the disease progression and neuroprotection of DR.

Keywords: apoptosis; autophagy; cellular senescence; computational biology; diabetic retinopathy (DR); differentially expressed genes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autophagy / genetics
Diabetic Retinopathy* / metabolism
Gene Expression Profiling / methods
Glucose / metabolism
Hyperglycemia* / genetics
Hyperglycemia* / metabolism
Rats
Retina / pathology

Substances

Glucose