The cell and molecular biology of glaucoma: axonopathy and the brain.
The cell and molecular biology of glaucoma: axonopathy and the brain.
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DOI：
10.1167/iovs.12-9483i
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发表时间：
2012-05-04
影响因子：
4.4
通讯作者：
Horner PJ
中科院分区：
文献类型：
--
作者：
Calkins DJ;Horner PJ
许多眼科医生和普通公众都将青光眼视为一种特殊的眼部疾病。这种观点已经（并且仍然）非常普遍，因为该疾病的病因涉及许多与眼睛相关的因素：眼压（IOP）、角膜厚度、视盘形态等。青光眼与眼压敏感性有关，通过局部应用降血压药物或手术来降低眼压是唯一的治疗形式。对青光眼动物模型的研究通常将眼压升高作为模拟与人类疾病相关的损伤的一种方式。然而，尽管控制眼内压可以减缓疾病进展，但它并不是治愈方法，而且尽管采取了降压治疗方案，青光眼的视力丧失往往仍然持续。 1 青光眼危害最大的是眼外部位，即视神经及其与大脑的连接发生退化。这一过程涉及视网膜神经节细胞 (RGC) 轴突的逐渐丧失，其中约 150 万个轴突构成了人类的视神经。实验模型中较小的眼睛相应地具有较少的轴突。轴突损失最终导致视网膜中 RGC 体细胞的凋亡消除。退化进展的速度取决于许多因素，包括治疗效果。在最坏的情况下，RGC 神经元及其在视神经投射中的连接的丧失代表着大脑的严重损伤。大约 50% 到 60% 的大脑皮层分布在 40 到 45 个不同的视觉区域，通过视神经处理来自视网膜的信息。从这个意义上说，青光眼是首要的与年龄相关的视神经病变，并且随着人口老龄化而变得更加普遍。由于视网膜和视神经是中枢神经系统的一部分，它们缺乏周围神经系统神经元有限但内在的自我修复能力。因此，寻找针对青光眼的新的神经中心疗法非常重要，不仅可以随着人口老龄化而保护视力，还可以转化为其他与年龄相关的脑部疾病（例如阿尔茨海默病和帕金森病）的新疗法。我们从神经生物学的角度在青光眼研究中学到的大部分知识现在正在为这些其他破坏性疾病的研究提供信息。 2
Many ophthalmologists and members of the lay public alike view glaucoma in its historical context—that is, as exclusively a disease of the eye. This view has been (and remains) overwhelmingly pervasive because the etiology of the disease involves so many factors associated with the eye: intraocular pressure (IOP), corneal thickness, optic disc morphology, and so on. Glaucoma is associated with sensitivity to IOP, and lowering IOP through either topical application of hypotensive drugs or surgery is the only form of treatment. Studies of animal models of glaucoma generally incorporate elevations in IOP as a way of mimicking the sort of injury that seems relevant to the human disease. However, although managing IOP can slow disease progression, it is not a cure, and vision loss in glaucoma often continues despite hypotensive regimens. 1 What is most damaging about glaucoma occurs outside of the eye, with degeneration of the optic nerve and its connections to the brain. This process involves the progressive loss of retinal ganglion cell (RGC) axons, some 1.5 million of which comprise the optic nerve in humans. Smaller eyes in experimental models have correspondingly fewer axons. Axon loss is followed eventually by apoptotic elimination of the RGC soma population in the retina. The rate at which degeneration progresses depends on many factors, including treatment efficacy. In the worst case, the loss of RGC neurons and their connections in the optic projection represents a substantial injury to the brain. Some 50% to 60% of the cerebral cortex spread over 40 to 45 distinct visual areas processes information from the retina via the optic nerve. In this sense, glaucoma is the premier age-related optic neuropathy and is becoming more prevalent as the population ages. Since the retina and optic nerve are part of the central nervous system, they lack the limited but intrinsic capacity of peripheral nervous system neurons for self-repair. Thus, identifying new neurocentric therapies for glaucoma is important, not only for preserving vision as the population ages, but also for translation to new treatments for other age-related brain diseases such as Alzheimer’s and Parkinson’s disease. Much of what we learn in glaucoma research from a neurobiological standpoint is now informing research for these other devastating conditions. 2
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影响因子：
4.5
作者：
Libby RT;Li Y;Savinova OV;Barter J;Smith RS;Nickells RW;John SW
通讯作者：
John SW
DBA/2J小鼠的进行性神经节细胞丧失和视神经变性是可变且不对称的。
影响因子：
2.4
作者：
Schlamp, Cassandra L.;Li, Yan;Dietz, Joel A.;Janssen, Katherine T.;Nickells, Robert W.
通讯作者：
Nickells, Robert W.
影响因子：
4.4
作者：
Calkins, David J.;Horner, Philip J.;Berkowitz, Bruce A.
通讯作者：
Berkowitz, Bruce A.
影响因子：
3.4
作者：
Burgoyne, Claude F.
通讯作者：
Burgoyne, Claude F.
影响因子：
5.7
作者：
Chan, Kevin C.;Li, Jiang;Wu, Ed X.
通讯作者：
Wu, Ed X.