生物谷報(bào)道：位于人類視網(wǎng)膜上數(shù)以百萬計(jì)的感光細(xì)胞可采集光線,，并將信號(hào)發(fā)送至大腦。 當(dāng)這些采集光線的細(xì)胞死亡后,，人的視力也隨之而去了,。 那些希望能扭轉(zhuǎn)失明進(jìn)程的醫(yī)學(xué)研究人員們將他們的目光投向了干細(xì)胞，最近的實(shí)驗(yàn)顯示這些細(xì)胞可替換因黃斑退化而損失的感光細(xì)胞,。
黃斑退化是最常見的失明原因,，在65歲以上的美國(guó)人中，有10%的人受這一病變的影響,。 黃斑退化的第一個(gè)目標(biāo)是一層被稱作視網(wǎng)膜色素上皮細(xì)胞（RPE）的保護(hù)層,，該保護(hù)層可將營(yíng)養(yǎng)轉(zhuǎn)運(yùn)給感光細(xì)胞，對(duì)感光細(xì)胞的存活至關(guān)重要,。 移植新鮮的視網(wǎng)膜色素上皮細(xì)胞組織能挽救正在死亡的感光細(xì)胞,。 但這一方法可行性并不高，因?yàn)橐委煍?shù)以百萬計(jì)的出現(xiàn)早期黃斑退化癥狀的美國(guó)人所需要的這種細(xì)胞組織數(shù)量是很大的,。
在位于馬塞諸塞州Worcester市的生物技術(shù)公司Advanced Cell Technology中工作的科學(xué)家們?yōu)橐暰W(wǎng)膜色素上皮細(xì)胞創(chuàng)造了一個(gè)更豐富的來源,。 2004年他們發(fā)明了一種方法可誘使胚胎干細(xì)胞轉(zhuǎn)變成為可移植的視網(wǎng)膜色素上皮細(xì)胞組織。 在接下來的實(shí)驗(yàn)中,，他們將轉(zhuǎn)變而來的細(xì)胞注入患有可造成感光細(xì)胞死亡的視網(wǎng)膜色素上皮細(xì)胞基因缺陷的大鼠眼內(nèi),。 據(jù)研究人員們發(fā)表在2006年12月的克隆與干細(xì)胞雜志上的報(bào)道稱，數(shù)周之后,，當(dāng)疾病造成的后果理應(yīng)出現(xiàn)的時(shí)候,，接受過治療的大鼠比未接受治療的大鼠在追蹤旋轉(zhuǎn)園柱上條紋的實(shí)驗(yàn)中表現(xiàn)要好兩倍。 它們的視力盡管得到了改善,，但仍遠(yuǎn)低于正常大鼠,。
但要治療患有高度黃斑退化或其它感光細(xì)胞疾病的患者，最終仍需要修復(fù)感光細(xì)胞本身,。 去年11月,，在University College London及其它機(jī)構(gòu)工作的研究人員們宣布，他們從處于不同發(fā)育階段的小鼠視網(wǎng)膜中提取細(xì)胞,，并已成功地將其移植到失明的小鼠身上,。 他們發(fā)現(xiàn)，從新生小鼠身上提取的未成熟的感光細(xì)胞,，而非從胚胎或成年小鼠身上提取的感光細(xì)胞,，可遷移到視網(wǎng)膜的正確區(qū)域，并且繼續(xù)發(fā)育成成熟的感光細(xì)胞,。 接受這些細(xì)胞的瞳孔對(duì)光的敏感度也高于那些未接受移植的瞳孔,。
在華盛頓大學(xué)從事視網(wǎng)膜發(fā)育研究的Thomas Reh表示,，這些發(fā)現(xiàn)提示，進(jìn)行細(xì)胞移植--比如感光細(xì)胞的移植時(shí),，被移植細(xì)胞的發(fā)育階段應(yīng)比干細(xì)胞要相對(duì)成熟一些,。 然而，與這種從新生小鼠身上提取的未成熟感光細(xì)胞相當(dāng)?shù)娜祟惣?xì)胞,，不得不改從胚胎的視網(wǎng)膜上分離出來,，造成一個(gè)相似的問題：尋找未成熟細(xì)胞的來源。 成人的干細(xì)胞和角膜干細(xì)胞是兩個(gè)其他可能產(chǎn)生未成熟感光細(xì)胞的來源,。
Reh在他的實(shí)驗(yàn)室中試圖使人類胚胎干細(xì)胞轉(zhuǎn)變成視網(wǎng)膜干細(xì)胞,，目前，有大約6%的胚胎干細(xì)胞轉(zhuǎn)變成了感光細(xì)胞,。 這一轉(zhuǎn)化率看起來很低,，但不必為低轉(zhuǎn)化率而感到泄氣，加州La Jolla的Burnham 醫(yī)學(xué)研究院的干細(xì)胞研究人員Evan Snyder認(rèn)為,。通過研究是什么促使這6%轉(zhuǎn)變成為感光細(xì)胞,，研究人員們有望找出如何造出更大數(shù)量的用于移植的細(xì)胞的方法。 他們有望找到一種方法,，可將需要的細(xì)胞從大量的混合細(xì)胞中挑選出來,。在位于Ann Arbor的密西根大學(xué)工作的眼科學(xué)研究人員 Anand Swaroop，正在集中精力開發(fā)一種方法,，通過細(xì)胞表面的蛋白鑒別出感光細(xì)胞,，并把它們挑出來。
找到制造細(xì)胞的來源,，并克服與干細(xì)胞移植有關(guān)的安全方面的顧慮后,，研究人員們還要面對(duì)他們最大的挑戰(zhàn)： 展示如何將移植的感光細(xì)胞與最終連接到視神經(jīng)上的其它神經(jīng)元相連。 每個(gè)感光細(xì)胞都必須完成數(shù)以百計(jì)的這種關(guān)鍵的連接,。 “僅僅擁有正確的細(xì)胞類型號(hào)并不意味著就已經(jīng)擁有了正確的神經(jīng)回路,，”Snyder說。 從小鼠視網(wǎng)膜移植的未成熟的感光細(xì)胞顯示其起作用了,，但Swaroop謹(jǐn)慎地說,，需要進(jìn)行行為試驗(yàn)以證實(shí)感光細(xì)胞已經(jīng)得以修復(fù)。 部分的連接即可產(chǎn)生在小鼠瞳孔試驗(yàn)中見到的那種活性,，但真正的視力改善則取決于實(shí)驗(yàn)動(dòng)物對(duì)顏色及其它視覺線索的反應(yīng)能力,。 畢竟，還是那句老話,，眼見為實(shí),。
來源： 科學(xué)美國(guó)人雜志
原文出處：
Progress in Cell Transplants to Heal Damaged Retinas
03/06/07 -- Millions of photoreceptor cells residing in the human retina gather light and transmit signals to the brain. When these light-collecting cells die, they take the person's sight with them. Medical researchers hoping to reverse blindness have turned their gaze toward stem cells, and recent experiments have shown that these cells could replace photoreceptors lost in macular degeneration.
As the most common form of blindness, macular degeneration affects 10 percent of Americans older than 65 years. It first targets a protective lining called the retinal pigment epithelium (RPE), which shuttles nutrients to the photoreceptor cells and is vital for their survival. A transplant of fresh RPE tissue could rescue dying photoreceptors. But the approach is not feasible considering the large amounts of tissue needed to treat the millions of Americans who show signs of early macular degeneration.
Scientists at the biotechnology firm Advanced Cell Technology in Worcester, Mass., have generated a more abundant source of RPE cells. In 2004 they devised a way to coax embryonic stem cells to turn into transplantable RPE tissue. In a follow-up experiment, they injected the transformed cells into the eyes of rats that had a photoreceptor-killing genetic defect in their RPE cells. As the researchers reported in the September 2006 Cloning and Stem Cells, weeks later, when the effects of the disease would have normally set in, the rats receiving the treatment were able to track stripes on a rotating cylinder twice as well as those that did not. Their vision, though improved, was still far below normal.
But treating patients who have advanced degrees of macular degeneration or other photoreceptor diseases will ultimately require repairing the photoreceptor cells themselves. Last November researchers at University College London and other institutions announced that they had extracted cells from mouse retinas that were at different developmental stages and successfully transplanted them into blind mice. They found that immature photoreceptor cells from healthy newborn mice, rather than embryonic or adult mouse cells, migrated to the correct region of the retina and continued to develop into mature photoreceptor cells. The pupils that received these cells were also more sensitive to light than those that did not receive the transplant.
These findings have suggested the development stages at which to transplant cells--for instance, photoreceptor cells need to be relatively more mature than stem cells, according to Thomas Reh, who studies retinal development at the University of Washington. The human equivalent to the mouse cells, however, would have to be isolated from fetal retinas, posing the familiar problem of finding a source for the immature cells. Adult stem cells and cornea stem cells are two other possible sources for generating immature photoreceptor cells.
In his lab, Reh coaxes human embryonic stem cells into retinal stem cells, and currently about 6 percent of them subsequently turn into photoreceptor cells. That yield may sound small, but a low percentage is not necessarily discouraging, according to Evan Snyder, a stem cell researcher at the Burnham Institute for Medical Research in La Jolla, Calif. By studying what pushes those 6 percent into their fate as photoreceptor cells, researchers might figure out how to generate a larger number of transplantable cells. They might also come up with a way to select the right cells out of a mixed population; Anand Swaroop, an ophthalmology researcher at the University of Michigan at Ann Arbor, is working on a way to identify and weed out the photoreceptor cells by focusing on proteins present on cell surfaces.
Having generated a cell source and overcome the safety concerns associated with transplanting stem cells, researchers still face possibly their biggest challenge: showing that the transplanted photoreceptors wire up to other neurons that eventually connect to the optic nerves. Each photoreceptor must make hundreds of critical connections. "Just because you have the right cell type doesn't mean you have the right circuitry," Snyder says. The immature photoreceptors transplanted from mouse retinas show activity, but Swaroop cautions that behavioral tests must determine that the photoreceptor cells are being repaired. A partial connection could generate the activity seen in the mice's pupils, but true vision improvement depends on the animals' ability to react to color and other visual cues. Seeing, after all, is believing.
Source: Scientific America
http://www.bio.com/newsfeatures/newsfeatures_research.jhtml?cid=26800026
