生物谷：英国科学家近日研究发现，老年人易患的阿尔海默病（即老年性痴呆，AD）与青光眼的病因之间存在着紧密的联系。该研究有助于开发治疗老年性痴呆与青光眼的新药物。相关论文发表在这一周的《美国国家科学院院刊》（PNAS）上。
青光眼会加大眼球内的压力，但是关于它的病因，科学家一直没有弄清楚。研究人员曾推测，可能是这种不断加大的压力破坏了一种向大脑传输信号的神经细胞，该细胞称为视网膜神经节细胞（RGC）。但是后来眼科专家发现，即使用药物控制住这种压力后，青光眼仍旧会继续恶化。另外一些针对青光眼患者的研究发现，这些患者的RGCs会比正常人产生更多的β-淀粉样肽（β-amyloid），它会积聚AD患者脑中的斑块。而且，患有AD的病人RGC更容易损坏，更容易失去视觉。
为了进一步研究这二者之间的关系，伦敦大学学院的眼科专家Francesca Cordeiro领导研究小组人工诱导大鼠患上了青光眼。结果发现，大鼠RGCs里的β-amyloid增加了，而它在已凋亡的RGCs里增加得更多。在另一个实验里，研究人员向正常大鼠的眼中注射了一种β-amyloid亚基，该亚基能毒害大鼠眼部的中枢神经系统。结果显示，注射的剂量越大，RGCs死亡得越多。
接下来，为了阻碍这些患上了青光眼的大鼠脑部形成斑块，Cordeiro和同事采取了三种方法，其中就包括目前临床上用来治疗AD的一种方法。结果发现，虽然每一种都能减少斑块的积累和RGC的死亡，但是将三者结合起来效果是最好的。
Cordeiro和研究小组据此得出结论认为，针对β-amyloid的药物可能对治疗青光眼有效。而β-amyloid导致斑块形成很可能就是导致患AD和青光眼的共同路径。
日本岐阜药科大学研究青光眼的Hideaki Hara表示，此次发现确定了AD和青光眼之间的联系。但是土耳其Kocaeli大学的神经学家Pervin Iseri却认为，β-amyloid将来很可能被证明并不与RGC的凋亡直接相关。要证明青光眼和AD的形成机制之间确实存在着直接的关系，更进一步的研究是必需的。（科学网 梅进/编译）
原始出处:
Published online before print August 7, 2007
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0703707104
OPEN ACCESS ARTICLE
Medical Sciences
Targeting amyloid- in glaucoma treatment
( combination therapy | neuroprotection | retinal ganglion cell apoptosis )
Li Guo *, Thomas E. Salt , Vy Luong , Nicholas Wood *, William Cheung *, Annelie Maass *, Giulio Ferrari *, Françoise Russo-Marie ¶, Adam M. Sillito , Michael E. Cheetham ||, Stephen E. Moss , Frederick W. Fitzke , and M. Francesca Cordeiro ***
*Glaucoma and Retinal Degeneration Research, Pathology, Visual Science, Cell Biology, and ||Molecular and Cellular Neuroscience, University College London Institute of Ophthalmology, Bath Street, London EC1V 9EL, United Kingdom; the Institute of Ophthalmology, University of Parma, Via Gramsci, 43100 Parma, Italy; ¶Institut Cochin, 22 rue Mechain, F-75014 Paris, France; and the **Glaucoma Research Group, Western Eye Hospital, London NW1 5QH, United Kingdom
Edited by N. Avrion Mitchison, University College London, London, United Kingdom, and approved June 28, 2007 (received for review April 23, 2007)
The development of the devastating neurodegenerative condition, Alzheimer's disease, is strongly associated with amyloid- (A) deposition, neuronal apoptosis, and cell loss. Here, we provide evidence that implicates these same mechanisms in the retinal disease glaucoma, a major cause of irreversible blindness worldwide, previously associated simply with the effects of intraocular pressure. We show that A colocalizes with apoptotic retinal ganglion cells (RGC) in experimental glaucoma and induces significant RGC apoptosis in vivo in a dose- and time-dependent manner. We demonstrate that targeting different components of the A formation and aggregation pathway can effectively reduce glaucomatous RGC apoptosis in vivo, and finally, that combining treatments (triple therapy) is more effective than monotherapy. Our work suggests that targeting the A pathway provides a therapeutic avenue in glaucoma management. Furthermore, our work demonstrates that the combination of agents affecting multiple stages in the A pathway may be the most effective strategy in A-related diseases.
