A new genetic therapy not only helped blind mice regain enough light sensitivity to distinguish flashing from non-flashing lights, but also restored light response to the retinas of dogs, setting the stage for future clinical trials of the therapy in humans.
In normal mice with working photoreceptors (PR driven), stimulating the retina produces a variety of responses in retinal ganglion cells, the output of the eye. This can be seen in the colorful lower square, where measurements of the activity of different retinal ganglion cells are shown in response to the same stimulation. This is because the retinal circuit mediates different operations. Photoswitches inserted into retinal ganglion cells (RGC) of blind mice produce much less variety of response (all evenly red means the cells fire at the same time), while blind mice with photoswitches inserted into bipolar cells (ON-BC driven) exhibit much more variety in their retinal response to light, closer to that of normal mice. Future chemical/gene therapy should probably focus on bipolar cells in order to capture this retinal processing before signals are relayed to the brain.
Credit: Isacoff & Flannery/UC Berkeley and Beltran/PennVet
These tools are now the basis of new UC Berkeley projects recently funded by NIH and NSF through President Obama’s BRAIN Initiative.