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| Gautam Awatramani in his AV俱乐部 laboratory. (Nick Pearce Photo) |
They may just have to update the famous nursery rhyme, "Three blind mice."
When Gautam Awatramani took time off to visit friend Botond Roska at his newly established lab in Switzerland, he never thought he鈥檇 be part of a scientific breakthrough: restoring sight in mice with ever-worsening eye diseases.
A year later, the work of Dr. Awatramani and his colleagues has been published in the prestigious science journal Nature Neuroscience. Dr. Awatramani and other neuroscientists developed a strategy to restore visual functions in mice with retinal degenerative diseases, a major advancement in retinal disease research.聽
Dr. Awatramani, assistant professor in the Department of Anatomy and Neurobiology at AV俱乐部, says the opportunity caught him by surprise: 鈥淚 had been doing brain research at UBC and was going to take a year off before coming to AV俱乐部,鈥� he says. 鈥淲hen I arrived at Botond鈥檚 lab, I realized we could do something really important. It was fascinating.鈥�
Retinal degeneration is a leading cause of blindness in humans and this research is a major step in visual function restoration. The disease results in the complete loss of photoreceptors that enable vision, thus causing blindness.
Dr. Awatramani, Pamela Lagali and David Balya worked with teams of researchers led by Dr. Roska at the Friedrich Miescher Institute in Switzerland and Constance Cepko of Harvard Medical School.
鈥淚t was an international collaborative effort between scientists with a range of expertise,鈥� says Dr. Awatramani. The researchers successfully restored visual functions in mice with retinal degeneration disease, and while not as good as normal mice, the blind mice responded to light whereas before treatment, they didn鈥檛.
鈥淚t鈥檚 the first time a rescue of visual function with this strategy has been accomplished.鈥�
The process uses two types of bipolar cells in the retina, ON bipolar and OFF bipolar cells. ON cells are affected by illumination and OFF cells by dimming. Their strategy expresses Channelrhodopsin, a novel, light-activated molecule found in green algae, into targeted ON cells creating artificial photoreceptors. This approach differs from current methods being developed in the US and Germany, that non-selectively stimulate output ganglion cells with miniature electrode implants, in attempts to mimic effects of light.
鈥淭he retina isn鈥檛 a simple screen that detects visual images and sends them to the brain. It鈥檚 a complex multiprocessing unit and visual information is largely decomposed into different features when it reaches the ganglion cells,鈥� says Dr. Awatramani. 鈥淲e developed a strategy expressing the molecule channelrhodopsin in bipolar cells that normally lie downstream from photoreceptors, thus allowing the remnant retinal circuits to perform their normal extractions.鈥�
The breakthrough has created a buzz in the neuroscience and ophthalmology community. 鈥淭his may be the technology that brings the breakthrough for prosthetic devices for restoration of vision,鈥� says Steve Barnes, director of the AV俱乐部 Neuroscience Institute. 鈥淚t may be possible to duplicate what the complex circuitry of the retina does for our vision, but without photoreceptors.鈥�
鈥淭hat one can target a specific cell type in the retina and make it light sensitive is a marvelous achievement,鈥� says John Dowling, professor of Neuroscience at Harvard. 鈥淣ature Neuroscience is a top journal and there will be much interest from the vision and ophthalmic research community.鈥�
While the solution for complete recovery of vision hasn鈥檛 been discovered, Dr. Awatramani believes this work will lead to a breakthrough. Human clinical trials, headed by leading European ophthalmologist Jose Sahel, will take place in Paris with the hope of restoring visual function in human retinal degenerative diseases.
Dr. Awatramani will continue research at AV俱乐部鈥檚 Retina and Optic Nerve Research laboratory and collaborate with Dr. Roska in Switzerland. He鈥檒l also work with pioneering genetic engineer Raj Awatramani at Northwestern University in Chicago.
The next steps include targeting OFF bipolar cells to restore greater visual function in both the brightening and dimming circuits: 鈥淲e鈥檙e only at the beginning. There鈥檚 still much research to be done,鈥� he notes.