生物谷：英國科學(xué)家近日研究發(fā)現(xiàn),，老年人易患的阿爾海默?。蠢夏晷园V呆,，AD）與青光眼的病因之間存在著緊密的聯(lián)系,。該研究有助于開發(fā)治療老年性癡呆與青光眼的新藥物。相關(guān)論文發(fā)表在這一周的《美國國家科學(xué)院院刊》（PNAS）上,。
青光眼會加大眼球內(nèi)的壓力,，但是關(guān)于它的病因,，科學(xué)家一直沒有弄清楚,。研究人員曾推測，可能是這種不斷加大的壓力破壞了一種向大腦傳輸信號的神經(jīng)細胞,，該細胞稱為視網(wǎng)膜神經(jīng)節(jié)細胞（RGC）,。但是后來眼科專家發(fā)現(xiàn)，即使用藥物控制住這種壓力后,，青光眼仍舊會繼續(xù)惡化,。另外一些針對青光眼患者的研究發(fā)現(xiàn)，這些患者的RGCs會比正常人產(chǎn)生更多的β-淀粉樣肽（β-amyloid），它會積聚AD患者腦中的斑塊,。而且,，患有AD的病人RGC更容易損壞，更容易失去視覺,。
為了進一步研究這二者之間的關(guān)系,，倫敦大學(xué)學(xué)院的眼科專家Francesca Cordeiro領(lǐng)導(dǎo)研究小組人工誘導(dǎo)大鼠患上了青光眼。結(jié)果發(fā)現(xiàn),，大鼠RGCs里的β-amyloid增加了,，而它在已凋亡的RGCs里增加得更多。在另一個實驗里,，研究人員向正常大鼠的眼中注射了一種β-amyloid亞基,，該亞基能毒害大鼠眼部的中樞神經(jīng)系統(tǒng)。結(jié)果顯示,，注射的劑量越大,，RGCs死亡得越多。
接下來,，為了阻礙這些患上了青光眼的大鼠腦部形成斑塊,，Cordeiro和同事采取了三種方法，其中就包括目前臨床上用來治療AD的一種方法,。結(jié)果發(fā)現(xiàn),，雖然每一種都能減少斑塊的積累和RGC的死亡，但是將三者結(jié)合起來效果是最好的,。
Cordeiro和研究小組據(jù)此得出結(jié)論認為,，針對β-amyloid的藥物可能對治療青光眼有效。而β-amyloid導(dǎo)致斑塊形成很可能就是導(dǎo)致患AD和青光眼的共同路徑,。
日本岐阜藥科大學(xué)研究青光眼的Hideaki Hara表示,，此次發(fā)現(xiàn)確定了AD和青光眼之間的聯(lián)系。但是土耳其Kocaeli大學(xué)的神經(jīng)學(xué)家Pervin Iseri卻認為,，β-amyloid將來很可能被證明并不與RGC的凋亡直接相關(guān),。要證明青光眼和AD的形成機制之間確實存在著直接的關(guān)系，更進一步的研究是必需的,。（科學(xué)網(wǎng) 梅進/編譯）
原始出處:
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.
