Optogenetic therapy shows promise for reversing acquired blindnessView gallery - 2 images
Across the world many millions of people suffer from inherited conditions that progressively degenerate the light-sensing cells in their eyes, and eventually send them blind. Recently, however, researchers from the University of Bern and the University of Gottingen have developed a way to possibly reverse this damage by using a newly-developed, light-sensitive protein embedded into other cells in the retina to restore vision.
Retinitis pigmentosa, age-related macular degeneration, and diabetic retinopathy are all conditions that progressively, but effectively, destroy light-sensing cells in the eye. Past treatments have attempted to reduce or stop these diseases before they progressed to full blindness using pharmaceutical methods, gene replacement therapy, or both. The results, however, have been mixed, as the treatments do little to actually fully restore sight due to a lack of low-level light sensitivity and physiological rejection.
The new optogenetic therapeutic approach shows significantly more promise in returning complete sight as it implants light-sensing proteins into the remaining, deep-seated retinal cells, effectively changing them into photoreceptors and restoring vision. And, unlike earlier optogenetic therapies, it does not require abnormally high – and possibly damaging – light intensities to work.
In detail, the researchers utilized the light-sensing protein, Opto-mGluR6, a chimeric protein (that is, one made up from different sources with functional properties derived from each of the original proteins) consisting of two retinal proteins that are not only physiologically compatible and unlikely to be rejected by the immune system, but are also much more resistant to bleaching and light attenuation often found in other photoreceptor proteins.
By inserting this protein in the cells deeper in the retina and in the same enzymatic pathway of the original photoreceptor cells, the researchers claim to have effectively restored daylight vision to mice suffering from retinitis pigmentosa. This, the researchers further assert, has resulted in the mice having high-light sensitivity and a fast (that is, normal) transmission response restored.
"We were asking the question, 'Can we design light-activatable proteins that gate specific signaling pathways in specific cells?'," said Dr. Sonja Kleinlogel of the University of Bern. "In other words, can the natural signalling pathways of the target cells be retained and just modified in a way to be turned on by light instead of a neurotransmitter released from a preceding neuron?"
In incorporating the remaining cells at the upper portion of the eye’s visual detection system – as close as possible to where the photoreceptors were – the new photoreceptor proteins are able to maximize the light received by the retina. In other words, whilst the photoreceptors may not be fully replaced with original ones, those that are created are, at least, in the best position to simulate the original functionality.
"The major improvement of the new approach is that patients will be able to see under normal daylight conditions without the need for light intensifiers or image converter goggles," said Dr. Kleinlogel. "And retaining the integrity of the intracellular enzymatic cascade through which native mGluR6 acts ensures consistency of the visual signal, as the enzymatic cascade is intricately modulated at multiple levels".
The research was recently detailed in the journal PLOS Biology.