青光眼的主要病理特征是视网膜神经节细胞（RGCs）的逐步丢失，目前认为凋亡是其主要的死亡形式，但阻断凋亡并不能完全阻止RGC的丢失，说明还存在其他的细胞死亡机制。坏死性凋亡（necroptosis）是一种新的细胞程序性坏死方式，已在炎症及感染性疾病中得到证实。我们的前期工作表明，坏死性凋亡相关蛋白RIPK3在大鼠急性视神经挫伤视网膜上表达增加，同时我们建立了慢性高眼压Tg-MYOCY437H转基因小鼠，本课题提出科学假说：1）坏死性凋亡（RIPK3/MLKL/necroptosis通路）参与了青光眼RGCs丢失；2）阻断坏死性凋亡将具有神经保护作用。本课题通过转基因小鼠模拟青光眼的发病，探讨坏死性凋亡在慢性高眼压引起的RGCs丢失中的作用，阻断坏死性凋亡有望成为青光眼有效的干预靶点。本研究首次将坏死性凋亡概念引入青光眼研究领域，是十分值得探索的课题。

The major pathologic characteristic of glaucoma is the progressive loss of retinal ganglion cells (RGCs). Currently, apoptosis is believed to be the main reason of RGCs loss. However, inhibiting apoptosis did not completely prevent the loss of the RGC in glaucoma, which means that other different mechanisms may be involved. Necroptosis is a form of non-apoptotic cell death driven by the receptor interacting protein kinase 3 (RIPK3) and its substrate, mixed lineage kinase domain-like (MLKL). Necroptosis has been found to play an important role in inflammation and infection related diseases. Our previous work showed that high expression of RIPK3 was found in the retina of optic nerve crush model, and we also have the transgenic mouse (Tg-MYOCY437H) which could simulate the progression loss of RGCs in primary open angle glaucoma. Based on above, we put forward our hypothesis: 1) necroptosis and induced inflammaiton were involved in loss of RGCs in glaucoma; 2) inhibition of necroptosis will have a neuroprotective function in glaucoma. In this study, we aim to use animal models and biotechnologies to verify our hypothesis. The purpose of this study is to provide a brand new view to the pathogenesis of glaucoma and a new target for the treatment of glaucoma.