Riddell Nina, Faou Pierre, Crewther Sheila G
Department of Psychology and Counselling, School of Psychology and Public Health, La Trobe University, Plenty Rd., Bundoora, Melbourne, VIC, 3083, Australia.
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Sciences, La Trobe University, Melbourne, VIC, Australia.
BMC Dev Biol. 2018 Aug 29;18(1):18. doi: 10.1186/s12861-018-0177-1.
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.
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.
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.
近视影响着全球约14亿人，且患病率正在上升。由离焦镜片诱导的动物模型在形态和相关遗传途径方面与人类近视表现出惊人的相似性。关于动物蛋白质组变化的了解较少。因此，本研究旨在增进对蛋白质途径对晶状体离焦反应的理解，重点是将表达变化与无晶状体对照发育相关联，并确定近视和远视（远视）模型中的双向和/或不同途径。
采用无标记定量蛋白质组学和基因集富集分析（GSEA）来检测用-10屈光度（D）镜片诱导近视6小时和48小时、用+10D镜片诱导远视或正常无晶状体饲养后雏鸡视网膜/视网膜色素上皮（RPE）中的蛋白质途径表达。在无晶状体雏鸡中，71条与细胞发育和神经元成熟相关的途径在6小时至48小时之间存在差异富集。这些正常发育变化中的大多数被佩戴镜片所破坏（71条途径中的47条），然而，只有11条途径在不同镜片条件下表现出不同的表达谱。最值得注意的是，在6小时至48小时之间，负镜片佩戴诱导了参与ATP驱动的离子转运、钙稳态和GABA信号传导相关蛋白质的上调，而在正常发育的雏鸡中，相同的蛋白质随时间下调。谷氨酸和碳酸氢盐/氯离子转运体在正常发育的雏鸡中也随时间下调，正镜片佩戴抑制了这种下调。
雏鸡视网膜/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。这些途径中的大多数进一步被佩戴镜片所破坏了这些途径中的大多数进一步被佩戴镜片所破坏。所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所示）、细胞离子稳态和相关能量资源之间存在密切相互作用。我们还为远视诱导过程中SLC介导的跨膜转运变化提供了新证据，这可能对视锥-双极突触信号传导产生影响。这些发现反映了神经传递和离子稳态紊乱在光学诱导屈光不正中的关键作用，并由我们的视网膜离子驱动外流（RIDE）模型所预测。
