生物谷報道：來自Pennsylvania大學的科學家們最近證實，用于恢復盲人視網(wǎng)膜活性的基因療法同樣可以恢復大腦視覺中樞的功能——這是產(chǎn)生視覺的關鍵區(qū)域,。
這一由Penn醫(yī)學院的神經(jīng)學助理教授Geoffrey K. Aguirre領導的多學科小組發(fā)現(xiàn),，基因療法可以恢復天生失明的動物的視網(wǎng)膜、視覺通路和視覺中樞反應,，并且可能對人類起到同樣的效果。
以上結(jié)果支持了用這一治療視網(wǎng)膜疾病的療法來進行其它治療?？茖W家使用功能核磁共振測量了發(fā)生了RPE65基因變異的失明小狗的大腦區(qū)域活性，RPE65是視黃醛等物質(zhì)循環(huán)的關鍵分子,。同樣的變異在人類中會導致Leber先天性失明,，或LCA,。這是已知的第一種可用基因療法治療的人類視力缺陷。
基因療法通過將能正常工作的RPE65基因?qū)胍暰W(wǎng)膜,，來恢復犬類眼睛的正常功能,。但是在這之前，科學家并不清楚大腦是否可以接受到這些畫面,。
小組發(fā)現(xiàn),，基因療法可以大大提高大腦視覺中樞對于光的反應。在失明4年的小狗中,，大腦視覺功能得到了恢復,，并且這種恢復在另一只小狗中已經(jīng)維持了至少2年半，這表明此種療法的持久性,。
Penn的科學家因此研究了同種失明的人類病人的大腦視覺中樞,。RPE65變異的年輕病人有著完整的視覺中樞通路和近乎正常的結(jié)構(gòu)。Penn小組同時發(fā)現(xiàn),，盡管這些LCA病人對于微弱的光線沒有反應,，但是對于明亮的光源他們的反應和正常人卻差不多。
相關英文原文：
Gene therapy awakens the brain despite blindness from birth
Researchers at the University of Pennsylvania have demonstrated that gene therapy used to restore retinal activity to the blind also restores function to the brain's visual center, a critical component of seeing. The multi-institutional study led by Geoffrey K. Aguirre, assistant professor of neurology in Penn's School of Medicine, shows that gene therapy can improve retinal, visual-pathway and visual-cortex responses in animals born blind and has the potential to do the same in humans.
"The retina of the eye captures light, but the brain is where vision is experienced," Aguirre said. "The traditional view is that blindness in infancy permanently alters the structure and function of the brain, leaving it unable to process visual information if sight is restored. We've now challenged that view."
The results support the potential for human benefit from retinal therapies aimed at restoring vision to those with genetic retinal disease. Researchers used functional MRI to measure brain activity in blind dogs born with a mutation in gene RPE65, an essential molecule in the retinoid-visual cycle. The same mutation causes a blindness in humans called Leber congenital amaurosis, or LCA. It is the first human eye-retinal disorder slated for gene therapy.
Gene therapy, performed by introducing a working copy of RPE65 into the retina, restored eye function in canines. Yet, it was previously unclear if the brain could "receive" the restored sight.
The team found that gene therapy to the eye dramatically increased responses to light within the visual cortex of the canine brain. The recovery of visual brain function occurred in a canine that had been blind for the first four years of its life, and recovery was found to persist in another dog for at least two-and-a-half years after therapy, suggesting a level of permanence to the treatment.
Penn scientists then studied the structure and function of the visual brain of human patients with the same form of blindness. Young adults with blindness from RPE65 mutation had intact visual brain pathways with nearly normal structure. The Penn team also found that, while the visual cortex of these patients with LCA did not respond to dim lights, the brain's reaction to brighter lights was comparable to that of individuals with normal sight.
"It seems these patients have the necessary brain pathways ready to go if their eyes start working again," Aguirre said.
The results of the current study are critical to these human clinical trials, led at Penn's Scheie Eye Institute by Samuel G. Jacobson, professor of ophthalmology, and Artur V. Cideciyan, research associate professor of ophthalmology.
"Existence of functional potential both in the eye and brain are prerequisites for successful gene therapy in all forms of LCA," Cideciyan said. "In the RPE65 form of the disease, we now have evidence for both, and treatment at the retinal level has the hope of recovery of useful vision in patients."
Findings of the study were reported in the journal PLoS Medicine.
原始出處：
Canine and Human Visual Cortex Intact and Responsive Despite Early Retinal Blindness from RPE65 Mutation
Geoffrey K. Aguirre1*, András M. Komáromy2, Artur V. Cideciyan3, David H. Brainard4, Tomas S. Aleman3, Alejandro J. Roman3, Brian B. Avants5, James C. Gee5, Marc Korczykowski1, William W. Hauswirth6, Gregory M. Acland7, Gustavo D. Aguirre2, Samuel G. Jacobson3
1 Department of Neurology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 2 Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 3 Department of Ophthalmology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 4 Department of Psychology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 5 Department of Radiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 6 Department of Ophthalmology, University of Florida, Gainesville, Florida, 7 Baker Institute, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America
Background
RPE65 is an essential molecule in the retinoid-visual cycle, and RPE65 gene mutations cause the congenital human blindness known as Leber congenital amaurosis (LCA). Somatic gene therapy delivered to the retina of blind dogs with an RPE65 mutation dramatically restores retinal physiology and has sparked international interest in human treatment trials for this incurable disease. An unanswered question is how the visual cortex responds after prolonged sensory deprivation from retinal dysfunction. We therefore studied the cortex of RPE65-mutant dogs before and after retinal gene therapy. Then, we inquired whether there is visual pathway integrity and responsivity in adult humans with LCA due to RPE65 mutations (RPE65-LCA).
