All roads lead to glaucoma: Induced retinal injury cascades contribute to a common neurodegenerative outcome
All roads lead to glaucoma: Induced retinal injury cascades contribute to a common neurodegenerative outcome
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DOI：
10.1016/j.exer.2018.11.005
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发表时间：
2019-06-01
影响因子：
3.4
通讯作者：
Sivak, Jeremy M.
中科院分区：
文献类型：
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作者：
Alqawlaq, Samih;Flanagan, John G.;Sivak, Jeremy M.
青光眼描述了一种独特的视神经病变，具有复杂的病因和各种相关的危险因素，但具有相似的病理终点。年龄、眼压升高、平均动脉压低、自身免疫性疾病等危险因素均与视网膜神经节细胞死亡和视神经头重塑有关。今天，眼压管理仍然是护理的标准，即使眼压升高不是青光眼的病因，尽管有效地控制了眼压，患者仍可能继续失明。一种将青光眼视为一种复杂的神经退行性疾病的当代观点已经形成，同时人们认识到需要新的疾病来修改视网膜治疗策略和改善结果。然而，引发疾病过程的风险因素和视网膜损伤反应之间的区别并不总是明确的。在这篇综述中，我们试图区分不同的触发因素，以及它们与随后主要的RGC损伤机制的关系。我们认为，不同的青光眼危险因素导致相似的视网膜和视神经损伤级联反应，包括氧化和代谢应激、神经胶质细胞反应性和改变的炎症反应，这些因素诱导共同的分子信号诱导RGC凋亡。该组织形成了一个连贯的疾病框架，并为治疗干预提供了保守的目标，而不限于特定的风险因素。
Glaucoma describes a distinct optic neuropathy with complex etiology and a variety of associated risk factors, but with similar pathological endpoints. Risk factors such as age, increased intraocular pressure (IOP), low mean arterial pressure, and autoimmune disease, can all be associated with death of retinal ganglion cells (RGCs) and optic nerve head remodeling. Today, IOP management remains the standard of care, even though IOP elevation is not pathognomonic of glaucoma, and patients can continue to lose vision despite effective IOP control. A contemporary view of glaucoma as a complex, neurodegenerative disease has developed, along with the recognition of a need for new disease modifying retinal treatment strategies and improved outcomes. However, the distinction between risk factors triggering the disease process and retinal injury responses is not always clear. In this review, we attempt to distinguish between the various triggers, and their association with subsequent key RGC injury mechanisms. We propose that distinct glaucomatous risk factors result in similar retinal and optic nerve injury cascades, including oxidative and metabolic stress, glial reactivity, and altered inflammatory responses, which induce common molecular signals to induce RGC apoptosis. This organization forms a coherent disease framework and presents conserved targets for therapeutic intervention that are not limited to specific risk factors.