BACKGROUND Myopia (short-sightedness) affects approximately 1.4 billion people worldwide, and prevalence is increasing. Animal models induced by defocusing lenses show striking similarity with human myopia in terms of morphology and the implicated genetic pathways. Less is known about proteome changes in animals. Thus, the present study aimed to improve understanding of protein pathway responses to lens defocus, with an emphasis on relating expression changes to no lens control development and identifying bidirectional and/or distinct pathways across myopia and hyperopia (long-sightedness) models. RESULTS Quantitative label-free proteomics and gene set enrichment analysis (GSEA) were used to examine protein pathway expression in the retina/RPE of chicks following 6 h and 48 h of myopia induction with - 10 dioptre (D) lenses, hyperopia induction with +10D lenses, or normal no lens rearing. Seventy-one pathways linked to cell development and neuronal maturation were differentially enriched between 6 and 48 h in no lens chicks. The majority of these normal developmental changes were disrupted by lens-wear (47 of 71 pathways), however, only 11 pathways displayed distinct expression profiles across the lens conditions. Most notably, negative lens-wear induced up-regulation of proteins involved in ATP-driven ion transport, calcium homeostasis, and GABA signalling between 6 and 48 h, while the same proteins were down-regulated over time in normally developing chicks. Glutamate and bicarbonate/chloride transporters were also down-regulated over time in normally developing chicks, and positive lens-wear inhibited this down-regulation. CONCLUSIONS The chick retina/RPE proteome undergoes extensive pathway expression shifts during normal development. Most of these pathways are further disrupted by lens-wear. The identified expression patterns suggest close interactions between neurotransmission (as exemplified by increased GABA receptor and synaptic protein expression), cellular ion homeostasis, and associated energy resources during myopia induction. We have also provided novel evidence for changes to SLC-mediated transmembrane transport during hyperopia induction, with potential implications for signalling at the photoreceptor-bipolar synapse. These findings reflect a key role for perturbed neurotransmission and ionic homeostasis in optically-induced refractive errors, and are predicted by our Retinal Ion Driven Efflux (RIDE) model.

中文翻译：

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短期光学散焦会干扰视网膜/ RPE蛋白丰度的正常发育变化。

背景技术近视（近视）影响全世界大约14亿人，并且患病率正在增加。由散焦透镜诱导的动物模型在形态和相关的遗传途径方面显示出与人类近视眼的惊人相似性。关于动物蛋白质组变化的了解较少。因此，本研究旨在增进对晶状体散焦的蛋白质途径反应的理解，重点在于将表达变化与无晶状体对照发展联系起来，并确定跨近视和远视（远视）模型的双向和/或独特途径。结果采用无标记的蛋白质组学和基因组富集分析（GSEA），通过10片屈光度（D）镜片诱导近视后6小时和48小时，检测了小鸡视网膜/ RPE中的蛋白质途径表达，+ 10D镜片进行远视诱导，或正常情况下无镜片饲养。在没有晶状体的小鸡中，与细胞发育和神经元成熟相关的71条途径在6到48小时之间差异性富集。这些正常的发育变化大部分受晶状体配戴的干扰（71条通路中的47条），但是，只有11条通路在整个晶状体条件下显示出不同的表达特征。最值得注意的是，负眼镜配戴会在6至48小时之间诱导参与ATP驱动的离子转运，钙稳态和GABA信号传导的蛋白质的上调，而正常发育的雏鸡中相同的蛋白质会随着时间而下调。在正常发育的雏鸡中，谷氨酸和碳酸氢盐/氯化物转运蛋白也随着时间而下调，并且正眼镜配戴抑制了这种下调。结论小鸡视网膜/ RPE蛋白质组在正常发育过程中经历了广泛的途径表达变化。眼镜佩戴会进一步破坏这些途径中的大多数。确定的表达模式表明在近视诱导过程中，神经传递（如GABA受体和突触蛋白表达增加），细胞离子稳态和相关能量之间存在密切的相互作用。我们还为远视诱导过程中SLC介导的跨膜运输的变化提供了新的证据，对光感受器-双极突触信号的潜在影响。这些发现反映了扰动的神经传递和离子稳态在光学诱发的屈光不正中的关键作用，并且由我们的视网膜离子驱动外流（RIDE）模型预测。