Retinal pathology in multiple sclerosis: insight into the mechanisms of neuronal pathology.
Retinal pathology in multiple sclerosis: insight into the mechanisms of neuronal pathology.
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DOI：
10.1093/brain/awq133
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发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Frohman EM
中科院分区：
文献类型：
--
作者：
Calabresi PA;Balcer LJ;Frohman EM
尽管多发性硬化症通常被指定为中枢神经系统的炎性脱髓鞘病症，但历史和现代描述已经强调轴突和神经元细胞体的参与与更完整地理解该疾病的病理生理学密切相关（Raine和Cross，1989; Ferguson等人，1997; Trapp等人，1998; Bitsch等人，2000; Peterson等人，2001; Lassmann，2004; Bruck，2005;豪瑟和Oksenberg，2006）。事实上，最近的研究已经产生了证实多发性硬化斑块病变中神经元凋亡的证据，以及皮质、海马和深灰质结构中氧化应激的迹象（Peterson et al.，2001; Bo等人，2003; Dutta等人，2006年）。几项研究表明，大脑皮层内疾病负荷的大小与多发性硬化症进行性表型的倾向之间存在对应关系（Kutzelnigg et al.，2005; Lassmann等人，2007年）。最近建立的灰质病变中炎性细胞浸润和胶质细胞活化的缺乏表明，灰质组织损伤的病理生物学基础可能不同于白色物质。特别是，灰质损伤可能主要是原发性神经元病理机制的衍生物，或者可能继发于间接影响，如轴突损伤和横断，最终导致神经元变性和体液损伤级联反应，包括抗体、细胞因子、蛋白酶、一氧化氮和谷氨酸（Rudick和Trapp，2009; Steinman，2009）。多发性硬化症神经元病理同时存在于眼睛和大脑中也不是新的原理，而是在过去几十年中没有进行广泛的病理学重新探索（Sharpe和Sanders，1975; Fisher等人，2006; Gordon-Lipkin等人，2007; Sepulcre等人，2007年; Waxman和Black，2007年）。眼睛炎症的发生，如多发性硬化症患者的视网膜静脉周围炎和葡萄膜炎所表现的，已经被认识了几十年，但只是最近才与神经纤维层损伤和脑萎缩有关。更令人感兴趣的是，尽管视网膜轴突是无髓鞘的，（髓磷脂是多发性硬化症疾病过程的假定靶点），多发性硬化症患者眼睛内的炎症活动证实了这种疾病中的免疫应答可能针对髓磷脂以外的抗原的假设，并建立了一个先例，积极探索创新的方法，将更充分地表征这些新的免疫反应库。最近，人们对前部视觉通路作为大脑窗口的兴趣重新抬头。高分辨率光学相干断层扫描的应用增加已经揭示，视网膜神经纤维层变薄在多发性硬化中是常见的，并且独立于视神经炎的病史而存在（Trip等人，2005; Fisher等人，2007; Gordon-Lipkin等人，2007年; Pullene等人，2007; Sepulcre等人，2007;亨德森等人，2008年）。支持这样的论点，即隐匿性疾病活动以类似于脑和脊髓组织损伤的方式靶向眼睛，原发性进行性多发性硬化症患者（没有任何种类的炎性脱髓鞘发作的那些）也表现出异常变薄的视网膜神经纤维层;并且视网膜神经纤维层厚度的纵向变化可以在有和没有视神经炎病史的患者中随时间测量（Pulpor等人，在本期《大脑》杂志中，绿色及其同事报告了对82例多发性硬化症患者的眼睛进行的尸检分析。
Although multiple sclerosis is commonly designated as an inflammatory demyelinating disorder of the central nervous system, historical and modern descriptions have underscored the involvement of axons and neuron cell bodies as germane to a more complete understanding of the pathophysiology of the disease (Raine and Cross, 1989; Ferguson et al., 1997; Trapp et al., 1998; Bitsch et al., 2000; Peterson et al., 2001; Lassmann, 2004; Bruck, 2005; Hauser and Oksenberg, 2006). Indeed, recent research has yielded evidence confirming neuronal apoptosis in multiple sclerosis plaque lesions, and signs of oxidative stress in cortex, hippocampus and deep grey matter structures (Peterson et al., 2001; Bo et al., 2003; Dutta et al., 2006). Several studies have suggested a correspondence between the magnitude of the disease burden within the cerebral cortex and the predilection for having a progressive phenotype of multiple sclerosis (Kutzelnigg et al., 2005; Lassmann et al., 2007). The recently established paucity of inflammatory cell infiltrates and glial cell activation in grey matter lesions suggests that the pathobiological underpinnings of tissue injury in grey matter may be distinctive from that of white matter. In particular, grey matter injury could principally be the derivative of a primary neuronal mechanism of pathology, or perhaps secondary to indirect influences such as axonal injury and transection, culminating in neuronal degeneration and humoral injury cascades including antibodies, cytokines, proteases, nitric oxide and glutamate (Rudick and Trapp, 2009; Steinman, 2009). That multiple sclerosis neuronal pathology concomitantly exists in the eye and brain is also not a new principle, but rather has escaped extensive pathological re-exploration in the past few decades (Sharpe and Sanders, 1975; Fisher et al., 2006; Gordon-Lipkin et al., 2007; Sepulcre et al., 2007; Waxman and Black, 2007). The occurrence of inflammation in the eye, as manifested by retinal periphlebitis and uveitis in patients with multiple sclerosis, has been recognized for many decades, but was only recently related to nerve fibre layer injury and brain atrophy. It is of further interest that, although retinal axons are unmyelinated (with myelin as the putative target of the disease process in multiple sclerosis), inflammatory activity within the eyes of patients with multiple sclerosis corroborates the hypothesis that the immune response in this disorder may be directed against antigens other than myelin, and establishes a precedent to explore actively innovative approaches that will characterize more fully these novel immune response repertoires. There has been a recent resurgence of interest in the anterior visual pathway as a window on the brain. The increased application of high-resolution optical coherence tomography has revealed that retinal nerve fibre layer thinning is a common occurrence in multiple sclerosis and exists independent of a history of optic neuritis (Trip et al., 2005; Fisher et al., 2007; Gordon-Lipkin et al., 2007; Pulicken et al., 2007; Sepulcre et al., 2007; Henderson et al., 2008). Bolstering the contention that occult disease activity targets the eye in a fashion similar to tissue injury in the brain and spinal cord, patients with primary progressive multiple sclerosis (those without inflammatory demyelinating attacks of any variety) also exhibit abnormally thinned retinal nerve fibre layers; and longitudinal changes in retinal nerve fibre layer thickness can be measured over time both in patients with and without a history of optic neuritis (Pulicken et al., 2007).In this issue of Brain, Green and colleagues report a post-mortem analysis of eyes from 82 cases of multiple sclerosis and …
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自身抗体靶标及其在副肿瘤性视网膜病的致病性中的癌症关系。
影响因子：
13.6
作者：
Adamus, Grazyna
通讯作者：
Adamus, Grazyna
DOI：
10.1073/pnas.0901496106
发表时间：
2009-05-19
影响因子：
11.1
作者：
Derfuss, Tobias;Parikh, Khyati;Meinl, Edgar
通讯作者：
Meinl, Edgar
影响因子：
4.1
作者：
SHARPE, JA;SANDERS, MD
通讯作者：
SANDERS, MD
影响因子：
3.6
作者：
Adamus, Grazyna;Brown, Lori;Weleber, Richard G.
通讯作者：
Weleber, Richard G.
影响因子：
9.9
作者：
Pulicken, M.;Gordon-Lipkin, E.;Calabresi, P. A.
通讯作者：
Calabresi, P. A.