Proceedings of the National Academy of Sciences · 2018 · 515 citations · 50 references
MedicineOphthalmologyVision ScienceCell SignalingGene ExpressionTranscriptomicsCellular Responses To HypoxiaGenetic Basis Of MyopiaPathophysiology Of MyopiaScleral PathologyScleral RemodelingHif-1 Alpha RegulationHypoxia-inducible Factor ActivationHypoxia-inducible Factor SignalingHypoxia-inducible SignalingMtor SignalingMyofibroblast DifferentiationMyopia-related Scleral RemodelingScleral Fibroblasts
) promoted myofibroblast transdifferentiation with down-regulation of type I collagen in human scleral fibroblasts. Importantly, the antihypoxia drugs salidroside and formononetin down-regulated HIF-1α expression as well as the phosphorylation levels of eIF2α and mTOR, slowing experimental myopia progression without affecting normal ocular growth in guinea pigs. Furthermore, eIF2α phosphorylation inhibition suppressed experimental myopia, whereas mTOR phosphorylation induced myopia in normal mice. Collectively, these findings defined an essential role of hypoxia in scleral ECM remodeling and myopia development, suggesting a therapeutic approach to control myopia by ameliorating hypoxia.
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