INSERM, U968, Paris, F-75012, France; UPMC Univ Paris 06, UMR_S968, Institut de la Vision, Paris, F-75012, France; CNRS, UMR_7210, Paris, F-75012, France.
CNRS, UMR_6270, PISSARO Proteomics Platform, Institute for Research and Innovation in Biomedicine, Rouen University, Mont Saint Aignan F-76821, France; INSERM, U905, PISSARO Proteomics Platform, Institute for Research and Innovation in Biomedicine, Rouen University Hospital, Rouen F-76000, France.
Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1242-1254. doi: 10.1016/j.bbadis.2017.03.022. Epub 2017 Mar 31.
High myopia (HM) is one of the main causes of visual impairment and blindness all over the world and an unsolved medical problem. Persons with HM are predisposed to other eye pathologies such as retinal detachment, myopic retinopathy or glaucomatous optic neuropathy, complications that may at least partly result from the extensive liquefaction of the myopic vitreous gel. To identify the involvement of the liquid vitreous in the pathogenesis of HM we here analyzed the vitreous of the recently described highly myopic low density lipoprotein receptor-related protein 2 (Lrp2)-deficient eyes. Whereas the gel-like fraction was not apparently modified, the volume of the liquid vitreous fraction (LVF) was much higher in the myopic eyes. Biochemical and proteome analysis of the LVF revealed several modifications including a marked decrease of potassium, sodium and chloride, of proteins involved in ocular tissue homeostasis and repair as well as of ADP-ribosylation factor 4 (ARF4), a protein possibly involved in LRP2 trafficking. A small number of proteins, mainly comprising known LRP2 ligands or proteins of the inflammatory response, were over expressed in the mutants. Moreover the morphology of the LRP2-deficient retinal pigment epithelium (RPE) cells was affected and the expression of ARF4 as well as of proteins involved in degradative endocytosis was strongly reduced. Our results support the idea that impairment of the RPE structure and most likely endocytic function may contribute to the vitreal modifications and pathogenesis of HM.
高度近视（HM）是全球视力损害和失明的主要原因之一，也是一个尚未解决的医学难题。高度近视患者易患其他眼部疾病，如视网膜脱离、近视性视网膜病变或青光眼性视神经病变，这些并发症至少部分可能是由于近视玻璃体凝胶的广泛液化所致。为了确定液体玻璃体在 HM 发病机制中的作用，我们在这里分析了最近描述的高度近视低密度脂蛋白受体相关蛋白 2（Lrp2）缺陷型眼睛的玻璃体。虽然凝胶状部分没有明显改变，但近视眼中液体玻璃体部分（LVF）的体积要高得多。LVF 的生化和蛋白质组分析显示了几种修饰，包括钾、钠和氯的明显减少，参与眼组织内稳态和修复的蛋白质以及 ADP-核糖基化因子 4（ARF4）的减少，ARF4 可能参与 Lrp2 的运输。LVF 中少量的蛋白质，主要包括已知的 Lrp2 配体或炎症反应的蛋白质，在突变体中过表达。此外，LRP2 缺陷型视网膜色素上皮（RPE）细胞的形态受到影响，ARF4 的表达以及参与降解性内吞作用的蛋白质的表达也明显减少。我们的结果支持这样一种观点，即 RPE 结构和很可能的内吞作用的损伤可能导致玻璃体的改变和 HM 的发病机制。
