Giummarra Loretta, Crewther Sheila G, Riddell Nina, Murphy Melanie J, Crewther David P
School of Psychology & Public Health, La Trobe University, Melbourne, Victoria, Australia.
Centre for Psychopharmacology, Swinburne University of Technology, Hawthorn, Victoria, Australia.
PeerJ. 2018 Jun 27;6:e5048. doi: 10.7717/peerj.5048. eCollection 2018.
RNA sequencing analysis has demonstrated bidirectional changes in metabolism, structural and immune pathways during early induction of defocus induced myopia. Thus, the aim of this study was to investigate whether similar gene pathways are also related to the more excessive axial growth, ultrastructural and elemental microanalytic changes seen during the induction and recovery from form-deprivation myopia (FDM) in chicks and predicted by the RIDE model of myopia.
Archived genomic transcriptome data from the first three days of induction of monocularly occluded form deprived myopia (FDMI) in chicks was obtained from the GEO database (accession # GSE6543) while data from chicks monocularly occluded for 10 days and then given up to 24 h of normal visual recovery (FDMR) were collected. Gene set enrichment analysis (GSEA) software was used to determine enriched pathways during the induction (FDMI) and recovery (FDMR) from FD. Curated gene-sets were obtained from open access sources.
Clusters of significant changes in mitochondrial energy metabolism, neurotransmission, ion channel transport, G protein coupled receptor signalling, complement cascades and neuron structure and growth were identified during the 10 days of induction of profound myopia and were found to correlate well with change in axial dimensions. Bile acid and bile salt metabolism pathways (cholesterol/lipid metabolism and sodium channel activation) were significantly upregulated during the first 24 h of recovery from 10 days of FDM.
The gene pathways altered during induction of FDM are similar to those reported in defocus induced myopia and are established indicators of oxidative stress, osmoregulatory and associated structural changes. These findings are also consistent with the choroidal thinning, axial elongation and hyperosmotic ion distribution patterns across the retina and choroid previously reported in FDM and predicted by RIDE.
RNA测序分析表明，在散焦诱导近视的早期诱导过程中，代谢、结构和免疫途径存在双向变化。因此，本研究的目的是调查在雏鸡形觉剥夺性近视（FDM）的诱导和恢复过程中，是否也有类似的基因途径与更过度的眼轴生长、超微结构和元素微分析变化相关，这些变化由近视的RIDE模型预测。
从GEO数据库（登录号#GSE6543）中获取雏鸡单眼形觉剥夺性近视（FDMI）诱导前三天的存档基因组转录组数据，同时收集单眼遮盖10天然后给予长达24小时正常视觉恢复（FDMR）的雏鸡数据。使用基因集富集分析（GSEA）软件确定从FD诱导（FDMI）和恢复（FDMR）过程中富集的途径。 curated基因集来自开放获取资源。
在深度近视诱导的10天内，发现线粒体能量代谢、神经传递、离子通道转运、G蛋白偶联受体信号传导、补体级联反应以及神经元结构和生长存在显著变化簇，并且发现这些变化与眼轴尺寸的变化密切相关。从10天的FDM恢复的前24小时内，胆汁酸和胆盐代谢途径（胆固醇/脂质代谢和钠通道激活）显著上调。
FDM诱导过程中改变的基因途径与散焦诱导近视中报道的途径相似，是氧化应激、渗透调节和相关结构变化的既定指标。这些发现也与先前在FDM中报道并由RIDE预测的脉络膜变薄、眼轴伸长以及视网膜和脉络膜上的高渗离子分布模式一致。
