Blindness is one of the most devastating conditions affecting the quality of life in developed countries, especially in Europe. No treatment is known today for retinal degenerative diseases, such as retinitis pigmentosa or macular degeneration. They are hereditary diseases characterized by the progressive loss of photoreceptors, leading to complete blindness. Recent discoveries of optical neuromodulators, such as channelrhodopsin-2 (ChR2) or halorhodopsin (NpHR), have opened up new possibilities of treating these diseases by imparting light-sensitivity to the remaining retinal neurons after the photoreceptors have died. During my previous Marie Curie postdoctoral fellowship, I have shown in a proof-of-concept study that this approach is feasible. We used a mouse model of retinal degeneration (rd1) and introduced ChR2 specifically in ON bipolar cells of the retina, upon which the animal regained retinal light responses, light-guided behavior, and form vision.
Here, I propose to test several optogenetic strategies of treating blindness. This includes the use of several different mouse models for retinal degeneration, in appreciation of the fact that degenerative diseases are very diverse and a single approach might not work for different conditions. For each model organism, I will test the effectiveness of rendering different cell types light sensitive with optogenetic tools. Examples include bipolar cells and subsets thereof, and ganglion cells. The optogenetic tools I will use include ChR2 which activates neurons upon light stimulation, and NpHR, which hyperpolarizes neurons.
The success of vision restoration will be tested and quantified at many levels, starting from the cellular level in the retina, to verify proper expression of the neuromodulator, to the circuitry level, to quantify the restoration of functional retinal properties, to the level of behavior, to establish if the animal regains visual guided behavior and form vision.
Field of science
- /medical and health sciences/clinical medicine/ophthalmology
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