Department of Psychology and Counselling, La Trobe University, Melbourne, VIC, Australia.
School of Health and Biomedical Sciences, RMIT, Melbourne, VIC, Australia.
Sci Rep. 2021 Mar 5;11(1):5280. doi: 10.1038/s41598-021-84338-y.
Currently there is no consensus regarding the aetiology of the excessive ocular volume that characterizes high myopia. Thus, we aimed to test whether the gene pathways identified by gene set enrichment analysis of RNA-seq transcriptomics refutes the predictions of the Retinal Ion Driven Efflux (RIDE) hypothesis when applied to the induction of form-deprivation myopia (FDM) and subsequent recovery (post-occluder removal). We found that the induction of profound FDM led to significant suppression in the ligand-gated chloride ion channel transport pathway via suppression of glycine, GABA and GABA ionotropic receptors. Post-occluder removal for short term recovery from FDM of 6 h and 24 h, induced significant upregulation of the gene families linked to cone receptor phototransduction, mitochondrial energy, and complement pathways. These findings support a model of form deprivation myopia as a Cl ion driven adaptive fluid response to the modulation of the visual signal cascade by form deprivation that in turn affects the resultant ionic environment of the outer and inner retinal tissues, axial and vitreal elongation as predicted by the RIDE model. Occluder removal and return to normal light conditions led to return to more normal upregulation of phototransduction, slowed growth rate, refractive recovery and apparent return towards physiological homeostasis.
目前，对于高度近视特征性的眼轴过度增长的病因尚未达成共识。因此，我们旨在测试 RNA 测序转录组学的基因集富集分析确定的基因途径是否与视网膜离子驱动外流（RIDE）假说的预测相矛盾，该假说应用于形觉剥夺性近视（FDM）的诱导及其随后的恢复（眼罩去除后）。我们发现，深度 FDM 的诱导导致通过抑制甘氨酸、GABA 和 GABA 离子型受体显著抑制配体门控氯离子通道转运途径。在 FDM 去除眼罩后 6 小时和 24 小时的短期恢复期间，与视锥细胞光转导、线粒体能量和补体途径相关的基因家族显著上调。这些发现支持了一种形觉剥夺性近视的模型，即 Cl 离子驱动的适应性流体反应，以适应由形觉剥夺引起的视觉信号级联的调制，进而影响外和内视网膜组织、轴向和玻璃体液的伸长，正如 RIDE 模型所预测的那样。眼罩去除并恢复正常光照条件后，光转导恢复到更正常的水平，生长速度减慢，屈光力恢复，生理稳态似乎得到恢复。
