Widespread Involvement of Acetylation in the Retinal Metabolism of Form-Deprivation Myopia in Guinea Pigs

Myopia has become the major cause of visual impairment
worldwide.
Although the pathogenesis of myopia remains controversial, proteomic
studies suggest that dysregulation of retinal metabolism is potentially
involved in the pathology of myopia. Lysine acetylation of proteins
plays a key role in regulating cellular metabolism, but little is
known about its role in the form-deprived myopic retina. Hence, a
comprehensive analysis of proteomic and acetylomic changes in the
retinas of guinea pigs with form-deprivation myopia was performed.
In total, 85 significantly differential proteins and 314 significantly
differentially acetylated proteins were identified. Notably, the differentially
acetylated proteins were markedly enriched in metabolic pathways such
as glycolysis/gluconeogenesis, the pentose phosphate pathway, retinol
metabolism, and the HIF-1 signaling pathway. HK2, HKDC1, PKM, LDH,
GAPDH, and ENO1 were the key enzymes in these metabolic pathways with
decreased acetylation levels in the form-deprivation myopia group.
Altered lysine acetylation of key enzymes in the form-deprived myopic
retina might affect the dynamic balance of metabolism in the retinal
microenvironment by altering their activity. In conclusion, as the
first report on the myopic retinal acetylome, this study provides
a reliable basis for further studies on myopic retinal acetylation.

近视已成为全球范围内视力损害的主要诱因。尽管近视的发病机制仍存在争议，但蛋白质组学研究表明，视网膜代谢失调可能参与近视的病理进程。蛋白质的赖氨酸乙酰化在调控细胞代谢中发挥关键作用，但目前对于其在形觉剥夺性近视视网膜中的作用尚不清楚。为此，本研究对形觉剥夺性近视豚鼠的视网膜开展了全面的蛋白质组学与乙酰化组学分析。本研究共鉴定出85个差异表达蛋白质及314个差异乙酰化蛋白质。值得注意的是，差异乙酰化蛋白质显著富集于糖酵解/糖异生、磷酸戊糖途径、视黄醇代谢以及缺氧诱导因子-1（HIF-1）信号通路等代谢通路中。HK2、HKDC1、PKM、LDH、GAPDH及ENO1为上述代谢通路中的关键酶，在形觉剥夺性近视组中其乙酰化水平均有所下调。形觉剥夺性近视视网膜内关键酶的赖氨酸乙酰化水平改变，可通过调控酶活性影响视网膜微环境的代谢动态平衡。综上，作为首项针对近视视网膜乙酰化组的研究，本研究为后续近视视网膜乙酰化相关研究提供了可靠的理论基础。