Investigation of the molecular mechanism of glaucoma and gene therapy for the treatment of glaucoma

在青光眼中，异常升高的眼内压（IOP）诱导视网膜神经节细胞死亡，导致视力丧失。目前，大多数青光眼药物和手术都是为了降低IOP而开发的。我们的实验研究旨在保护视网膜神经节细胞死亡的“神经保护疗法“和修复受损轴突的“神经再生疗法”。“为了拯救视网膜神经节细胞免于细胞死亡，我们研究了神经营养因子在动物青光眼模型中的神经保护作用。免疫组化结果显示，在动物视网膜胶质瘤模型中，Muller胶质细胞和星形胶质细胞被激活，并分泌睫状神经营养因子（ciliary neurotrophic factor，CNTF）。此外，两种类型的神经营养因子，睫状神经营养因子（CNTF）和脑源性神经营养因子（BDNF）显示神经保护作用的视网膜神经节细胞在动物脑胶质瘤模型。此外，我们证明了两种类型的硫酸软骨素蛋白聚糖（CSPGs），神经聚糖和磷酸蛋白聚糖，在发育中的视网膜中高度表达。此外，CSPGs在体外调节视网膜神经节细胞的神经突起生长，表明通过控制CSPGs的表达可以实现神经再生治疗的可能性。我们的研究将在发展青光眼治疗的新概念中发挥重要作用。

In glaucomatous eyes, abnormally increased intraocular pressure (IOP) induces retinal ganglion cell death, resulting in loss of visual acuity. At present, most of the drugs and surgeries for glaucoma have been developed for lowering IOPs. Our experimental studies are aimed to protect the cell death of retinal ganglion cells, "neuroprotective therapy, "and repair the damaged axons, "neuroregenerative therapy." In an attempt to rescue retinal ganglion cells from cell death, we investigated the neuroprotective effects of neurotrophic factors in animal glaucomatous models. Our immunohistochemical analyses showed that, in the retinal tissues of animal glaucomatous models, Muller glial cells and astrocytes were activated, and one of neurotrophic factors, ciliary neurotrophic factor (CNTF), was secreted from these glial cells. Moreover, two types of neurotrophic factors, ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) showed neuroprotective effects for retinal ganglion cells in animal glaucomatous models. In addition, we demonstrated that two types of chondroitin sulfate proteoglycans (CSPGs), neurocan and phosphacan, were highly expressed in the developing retina. Furthermore, the CSPGs regulated the neurite outgrowth from retinal ganglion cells in vitro, indicating the possibility that the neuroregenerative therapy can be achieved by controlling the expression of the CSPGs. Our investigations will play important roles in developing the new concepts of the treatment for glaucoma.