美國(guó)科學(xué)家將從海藻中提取出的基因注入失明老鼠視網(wǎng)膜內(nèi)的雙極細(xì)胞中,，讓失明老鼠“重見(jiàn)天日”,。科學(xué)家表示,，人體臨床試驗(yàn)將于兩年內(nèi)進(jìn)行,，新技術(shù)或?qū)⒃旄V大失明人士。研究將發(fā)表在《分子治療》雜志上,。
視網(wǎng)膜包含感光細(xì)胞,、雙極細(xì)胞和神經(jīng)節(jié)細(xì)胞。感光細(xì)胞將光量子能量轉(zhuǎn)換成電信號(hào)并傳到雙極細(xì)胞,，雙極細(xì)胞將信號(hào)處理后經(jīng)化學(xué)突觸傳遞到神經(jīng)節(jié)細(xì)胞,，神經(jīng)節(jié)細(xì)胞再將視網(wǎng)膜處理后的視覺(jué)信息編碼為神經(jīng)脈沖傳輸?shù)酱竽X。全球約有1500萬(wàn)名失明患者的視網(wǎng)膜內(nèi)感光細(xì)胞受損,，導(dǎo)致大腦無(wú)法接收?qǐng)D像信息,。
南加州大學(xué)洛杉磯分校遺傳醫(yī)學(xué)研究所的神經(jīng)學(xué)家阿蘭·霍薩格團(tuán)隊(duì)所使用的方法基于基因療法。在實(shí)驗(yàn)中,，他們用一個(gè)“馴化”病毒將單細(xì)胞海藻的一種基因運(yùn)送至失明老鼠的雙極細(xì)胞內(nèi),，讓其制造出了第二型離子通道視紫質(zhì)蛋白（ChR2，海藻使用該光敏蛋白幫助它們朝光移動(dòng)）,。修改后的雙極細(xì)胞能感光并將信號(hào)傳送給神經(jīng)節(jié)細(xì)胞,，讓實(shí)驗(yàn)老鼠恢復(fù)了感知光和黑暗的能力。
霍薩格團(tuán)隊(duì)使用三組實(shí)驗(yàn)鼠測(cè)試了該技術(shù)：一組實(shí)驗(yàn)鼠視力正常,，另兩組實(shí)驗(yàn)鼠失明,。科學(xué)家對(duì)其中一組失明實(shí)驗(yàn)鼠使用了基因療法,，向雙極細(xì)胞注入了包含有海藻基因的病毒,；另外兩組實(shí)驗(yàn)鼠不使用任何療法。10周后,，研究團(tuán)隊(duì)發(fā)現(xiàn),，雙極細(xì)胞制造出了ChR2蛋白。
實(shí)驗(yàn)中,，科學(xué)家將失明老鼠放入一個(gè)水迷宮的中央,，該水迷宮有六條可能的通道，其中一條通路內(nèi)包含有一個(gè)有助于老鼠逃跑的突起物,，一束引導(dǎo)光照耀在該通路的終點(diǎn),，最終，接受基因療法的老鼠發(fā)現(xiàn)逃逸平臺(tái)的速度是沒(méi)有接受基因療法的失明老鼠的2.5倍,。重復(fù)該測(cè)試10個(gè)月后,，該團(tuán)隊(duì)發(fā)現(xiàn),，接受基因療法的老鼠視力明顯有所改進(jìn)。
科學(xué)家認(rèn)為,，隨著全球老齡化趨勢(shì)不斷加劇,，失明人士將與日俱增?？茖W(xué)家正著手治療失明,，其中包括研制電子植入設(shè)備、用干細(xì)胞培育新的視網(wǎng)膜組織等,，但目前,，這些方法在商業(yè)上都不太可行，霍薩格希望最新研究能改變這種狀況,。
以前,，人們一直擔(dān)心基因療法的安全性，尤其是通過(guò)病毒運(yùn)送基因的療法,?；羲_格表示，海藻基因僅在視網(wǎng)膜的雙極細(xì)胞中表達(dá),，實(shí)驗(yàn)鼠沒(méi)有出現(xiàn)免疫反應(yīng),，這表明，外來(lái)基因僅被限于轉(zhuǎn)運(yùn)到雙極細(xì)胞內(nèi),。然而,，科學(xué)家在老鼠的其他組織內(nèi)發(fā)現(xiàn)了少量的ChR2基因，美國(guó)先進(jìn)細(xì)胞科技公司的首席科學(xué)家羅伯特·蘭薩表示：“監(jiān)管機(jī)構(gòu)會(huì)非常在意雙極細(xì)胞外發(fā)現(xiàn)的ChR2基因,。”（生物谷Bioon.com）
生物谷推薦原文出處：
Molecular Therapy , (19 April 2011) | doi:10.1038/mt.2011.69
Virally delivered Channelrhodopsin-2 Safely and Effectively Restores Visual Function in Multiple Mouse Models of Blindness
M Mehdi Doroudchi, Kenneth P Greenberg, Jianwen Liu, Kimberly A Silka, Edward S Boyden, Jennifer A Lockridge, A Cyrus Arman, Ramesh Janani, Shannon E Boye, Sanford L Boye, Gabriel M Gordon, Benjamin C Matteo, Alapakkam P Sampath, William W Hauswirth and Alan Horsager
AbstractPrevious work established retinal expression of channelrhodopsin-2 (ChR2), an algal cation channel gated by light, restored physiological and behavioral visual responses in otherwise blind rd1 mice. However, a viable ChR2-based human therapy must meet several key criteria: (i) ChR2 expression must be targeted, robust, and long-term, (ii) ChR2 must provide long-term and continuous therapeutic efficacy, and (iii) both viral vector delivery and ChR2 expression must be safe. Here, we demonstrate the development of a clinically relevant therapy for late stage retinal degeneration using ChR2. We achieved specific and stable expression of ChR2 in ON bipolar cells using a recombinant adeno-associated viral vector (rAAV) packaged in a tyrosine-mutated capsid. Targeted expression led to ChR2-driven electrophysiological ON responses in postsynaptic retinal ganglion cells and significant improvement in visually guided behavior for multiple models of blindness up to 10 months postinjection. Light levels to elicit visually guided behavioral responses were within the physiological range of cone photoreceptors. Finally, chronic ChR2 expression was nontoxic, with transgene biodistribution limited to the eye. No measurable immune or inflammatory response was observed following intraocular vector administration. Together, these data indicate that virally delivered ChR2 can provide a viable and efficacious clinical therapy for photoreceptor disease-related blindness.
