Abstract
Purpose :
High-altitude retinopathy (HAR) is initiated by hypobaric hypoxia and characterized by retinal function deficits. However, the exact molecular mechanisms involved in HAR remain incompletely understood. Our current investigation is to utilize the proteomic analysis to profile the proteomic changes in rat retina exposed to hypobaric hypoxia and evaluated the protective efficacy of hesperidin (HSD) on the hypobaric hypoxia-induced impairment to the retina.
Methods :
In the present study, we undertook an approach to mimic 5000m altitude with a low-pressure oxygen cabin. SD rats were randomized into control group, hypobaric hypoxia (HH), and HSD intervention group. Retinas were dissected following different treatments for 7 days. A quantitative comparison of the proteome in the retina was performed through TMT labeling, HPLC fractionation, LC-MS/MS and PRM analysis.
Results :
A total of 154 and 259 proteins were upregulated, 216 and 54 proteins were downregulated when compared the HH group with the control, HSD with HH group respectively. Subcellular distribution of deferentially expressed proteins were mostly localized in the cytoplasm, nucleus, followed by extracellular, plasma membrane and mitochondrion. Hypobaric hypoxia-triggered down-regulation of proteins in the retina were mainly related with cellular process, biologic regulation, stimulus response, multicellular-organismal process, metabolic and developmental process. HSD dramatically inhibited the hypobaric hypoxia-induced stress by upregulation of proteins mainly associated with the above-mentioned biological activities. Proteins inculding glial fibrillary acidic protein(GFAP), aldehyde dehydrogenase,dimeric NADP-preferring (ALDH3A1), neurofilament light polypeptide (NEFL), collagen alpha-1(Colla1) were downregulated in the hypobric hypoxic condition but enhanced by HSD intervention, which were validated by PRM assay. ECM-receptor interaction and PI3K-Akt signaling pathway were identified to be the most relevant pathways related with retina affected by either hypobaric hypoxia or HSD intervention through the KEGG pathway enrichment analysis.
Conclusions :
Our proteomic analysis suggests that hypobaric hypoxia exerts a pathological impact on the rat retina through affecting protein function. The intervention of HSD elicits a protective response to the hypobaric hypoxia-induced stress on the rat retina.
This is a 2021 ARVO Annual Meeting abstract.