Proteomic and Morphological Profiling of Mice Ocular Tissue During High-altitude Acclimatization Process: An Animal Study at Lhasa

Abstract

Jun Hou,1,* Dezhi Zheng,2,* Xudong Wen,3,* Wenjing Xiao,4 Fei Han,5 Hongmei Lang,6 Shiqiang Xiong,1 Wei Jiang,5 Yonghe Hu,4 Mengshan He,7 Pan Long4,5 1Department of Cardiology, Chengdu Third People’s Hospital/Affiliated Hospital of Southwest Jiaotong University, Chengdu, People’s Republic of China; 2Department of Cardiovascular Surgery, the 960th Hospital of the PLA Joint Logistic Support Force, Jinan, People’s Republic of China; 3Department of Gastroenterology and Hepatology, Chengdu First People’s Hospital, Chengdu, People’s Republic of China; 4School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, People’s Republic of China; 5Department of Ophthalmology, the General Hospital of Western Theater Command, Chengdu, People’s Republic of China; 6The Center of Obesity and Metabolic Diseases, Department of General Surgery, Chengdu Third People’s Hospital & the Affiliated Hospital of Southwest Jiaotong University, Chengdu, People’s Republic of China; 7Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Pan Long, Department of Ophthalmology, the General Hospital of Western Theater Command, Rongdu Avenue #270, Chengdu, People’s Republic of China, Tel [phone], Email [email protected] Yonghe Hu, School of Materials Science and Engineering, Southwest Jiaotong University, No. 111, North First Section of the Second Ring Road, Chengdu, People’s Republic of China, Tel [phone], Email [email protected]: High-altitude environment mainly with hypobaric hypoxia could induce pathological alterations in ocular tissue. Previous studies have mostly focused on sporadic case reports and simulated high-altitude hypoxia experiments. This aim of this study was to explore the proteomic and morphological changes of ocular tissue in mice at real altitude environment.Methods: In this study, mice were flown from Chengdu (elevation: 500 m) to Lhasa (elevation: 3600 m). After exposure for 1day, 3, 6, 10, 20, 30, and 40days, the mice were euthanatized to obtain blood and ocular tissue. Serological tests, ocular pathological examinations, integral ocular proteomics analysis, and Western blot were conducted.Results: We focused on acute phase (1– 3 days) and chronic phase (> 30 days) during high-altitude acclimatization. Serum interleukin-1 was increased at 3 days, while superoxide dismutase, interleukin-6, and tumor necrosis factor-α showed no statistical changes. H&E staining demonstrated that the cornea was edematous at 3 days and exhibited slower proliferation at 30 days. The choroid showed a consistently significant thickening, while there existed no noticeable changes in retinal thickness. Overall, 4073 proteins were identified, among which 71 and 119 proteins were detected to have significant difference at 3 days and 40 days when compared with the control group. Functional enrichment analysis found the differentiated proteins at 3 days exposure functionally related with response to radiation, dephosphorylation, negative regulation of cell adhesion, and erythrocyte homeostasis. Moreover, the differential profiles of the proteins at 40 days exposure exhibited changes of regulation of complement activation, regulation of protein activation cascade, regulation of humoral immune response, second-messenger-mediated signaling, regulation of leukocyte activation, and cellular iron homeostasis. Interestingly, we found the ocular proteins with lactylation modification were increased along high-altitude adaptation.Conclusion: This is the first work reporting the ocular proteomic and morphological changes at real high-altitude environment. We expect it would deep the understanding of ocular response during altitude acclimatization.Keywords: altitude response, ocular proteomics analysis, cornea edema, choroid thickening, post-translational modification

Keywords

• altitude response
• ocular proteomics analysis
• cornea edema
• choroid thickening
• post-translational modification