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

Abstract

Purpose 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.

Protein Lactylation Profiles Provide Insights into Molecular Mechanisms Underlying Metabolism in Yak

“…5 After prolonged exposure to high altitudes, lactylated proteins in the ocular tissues of mice have been observed to increase compared to those residing at low altitudes. 15 Similarly, the lactylated proteins identified in yaks exhibit a widespread involvement in metabolic processes across various tissues. Specifically, in the heart and muscles, these modified proteins are primarily associated with cardiac muscle contraction, the HIF-1 signaling pathway, and thermogenesis.…”

“…Notably, in MCF-7 cells, hypoxia induces elevated lactate production and histone lactylation levels . After prolonged exposure to high altitudes, lactylated proteins in the ocular tissues of mice have been observed to increase compared to those residing at low altitudes . Similarly, the lactylated proteins identified in yaks exhibit a widespread involvement in metabolic processes across various tissues.…”

“…14 Conversely, mice adapted to high-altitude conditions in the Qinghai−Tibetan Plateau exhibit elevated occular protein lactylation after prolonged exposure. 15 Both lactylated histones and nonhistones play a crucial role in regulating biological processes and metabolism. For instance, lactate-induced H3K9 lactylation modulates myogenic cell differentiation.…”

“…In vitro studies indicate that hypoxia reduces histone lactylation in mouse embryos, adversely affecting their preimplantation developmental potential . Conversely, mice adapted to high-altitude conditions in the Qinghai–Tibetan Plateau exhibit elevated occular protein lactylation after prolonged exposure …”