Retinal ganglion cell apoptosis in glaucoma is related to intraocular pressure and IOP-induced effects on extracellular matrix.
Retinal ganglion cell apoptosis in glaucoma is related to intraocular pressure and IOP-induced effects on extracellular matrix.
复制标题
青光眼中的视网膜神经节细胞凋亡与眼内压和IOP诱导的细胞外基质有关。
DOI：
10.1167/iovs.04-0832
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发表时间：
2005-01
影响因子：
4.4
通讯作者：
Cordeiro MF
中科院分区：
文献类型：
--
作者：
Guo L;Moss SE;Alexander RA;Ali RR;Fitzke FW;Cordeiro MF
目的探讨高眼压对大鼠视网膜神经节细胞（retinal ganglion cell，RGC）凋亡的影响及其与视网膜和视神经乳头（optic nerve head，ONH）细胞外基质（extracellular matrix，ECM）变化的关系。通过高渗盐水巩膜外静脉注射，37只Dark Agglomerate大鼠左眼出现IOP升高。在3个月时对眼睛进行组织学检查，以检测RGC凋亡和特定ECM组分的表达。RGC凋亡与眼压暴露量显著相关（积分ΔIOP P < 0.001;峰值IOP P < 0.01）。RGC层MMP-9活性（P < 0.001）、TIMP-1（P <0.05）、I型胶原（P <0.01）与眼压升高呈正相关，层粘连蛋白（P <0.05）、TGF-β2（P <0.05）与眼压升高呈负相关。MMP-9活性与RGC凋亡（P < 0.001）和层粘连蛋白丢失（P < 0.01）均呈显著相关。眼压暴露后ONH处TGF-β2和I型胶原沉积增加（P < 0.01）。结果表明，青光眼中的RGC凋亡与IOP升高密切相关，并且与IOP诱导的RGC层中特定ECM组分的变化显著相关。该研究首次显示了MMP-9、层粘连蛋白降解、RGC凋亡和青光眼中IOP暴露之间的联系。研究结果表明，在青光眼视网膜中异常ECM重塑可能与RGC死亡有关，并支持视网膜是青光眼损伤的主要部位的观点。
To investigate the effect of IOP on retinal ganglion cell (RGC) apoptosis and correlate the effects with IOP-induced changes in extracellular matrix (ECM) in the retina and optic nerve head (ONH) in glaucomatous rat eyes. Thirty-seven Dark Agouti rats had elevated IOP induced in the left eye by hypertonic saline episcleral vein injections. Eyes were examined at 3 months histologically for RGC apoptosis and expression of specific ECM components. RGC apoptosis was significantly related to IOP exposure (integral ΔIOP P < 0.001; peak IOP P < 0.01). In the RGC layer, elevated IOP correlated positively to a significant increase in MMP-9 activity (P < 0.001), tissue inhibitor of matrix metalloproteinase (TIMP-1) (P < 0.05), and collagen I (P < 0.01), and negatively correlated to deposition of laminin (P < 0.05) and TGF-β2 (P < 0.05). There was a significant correlation between MMP-9 activity and both RGC apoptosis (P < 0.001) and loss of laminin (P < 0.01). IOP exposure was also associated with increased deposition of TGF-β2 and collagen I at the ONH (P < 0.01). The results demonstrated that RGC apoptosis in glaucoma correlates strongly with elevated IOP and is significantly associated with IOP-induced changes in specific ECM components in the RGC layer. The study shows for the first time a link between MMP-9, laminin degradation, RGC apoptosis, and IOP exposure in glaucoma. The findings suggest that abnormal ECM remodeling in the glaucomatous retina may relate to RGC death and support the notion that the retina is a primary site of injury in glaucoma.