Optogenetic therapy shows promise for reversing acquired blindness
Acrossthe world many millions of people suffer from inherited conditions that progressivelydegenerate the light-sensing cells in their eyes, and eventually send themblind. Recently, however, researchers fromthe University of Bern and the University of Gottingen have developeda way to possibly reverse this damage by using a newly-developed, light-sensitiveprotein embedded into other cells in the retina to restore vision.
Retinitis pigmentosa, age-related macular degeneration, and diabeticretinopathy 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 progressedto full blindness using pharmaceutical methods, gene replacement therapy, orboth. The results,however, have been mixed, as the treatments do little to actually fully restoresight due to a lack of low-level light sensitivity and physiological rejection.
The new optogenetictherapeutic approach shows significantly more promise in returningcomplete sight as it implants light-sensing proteins into the remaining,deep-seated retinal cells, effectively changing them into photoreceptors and restoringvision. And, unlike earlier optogenetic therapies, it does not requireabnormally high – and possibly damaging – light intensities to work.
Indetail, the researchers utilized the light-sensing protein, Opto-mGluR6, achimeric protein (that is, one made up from different sources with functional properties derived fromeach of the original proteins) consisting of two retinalproteins that are not only physiologically compatible and unlikely to berejected by the immune system, but are also much more resistant to bleachingand light attenuation often found inother photoreceptor proteins.
Byinserting this protein in the cells deeper in the retina and in the sameenzymatic pathway of the original photoreceptor cells, the researchers claim tohave effectively restored daylight vision to mice suffering from retinitispigmentosa. This, the researchers further assert, has resulted in the micehaving high-light sensitivity and a fast (that is, normal) transmissionresponse restored.
"We were asking the question, 'Can wedesign light-activatable proteins that gate specific signaling pathways inspecific cells?'," said Dr.Sonja Kleinlogel of the University of Bern. "In other words, can the natural signalling pathways of thetarget cells be retained and just modified in a way to be turned on by lightinstead of a neurotransmitter released from a preceding neuron?"
In incorporating the remainingcells at the upper portion of the eye’s visual detection system – as closeas possible to where the photoreceptors were – the new photoreceptor proteins areable to maximize the light received by the retina. In other words, whilst thephotoreceptors may not be fully replaced with original ones, those that arecreated are, at least, in the best position to simulate the originalfunctionality.
"The major improvement ofthe new approach is that patients will be able to see under normal daylightconditions without the need for light intensifiers or image converter goggles,"said Dr. Kleinlogel. "And retaining the integrity of the intracellular enzymaticcascade through which native mGluR6 acts ensures consistency of the visualsignal, as the enzymatic cascade is intricately modulated at multiplelevels".
The research was recently detailed in the journal PLOS Biology.