Retinale Implantate

Projekt P3 - Recreating retinal output diversity in blind rd10 mice using optogenetics

01.12.2020 bis 30.11.2022

In an aging population, an increasing number of patients suffer from blindness due to dege-nerative diseases like Retinitis Pigmentosa (RP). Aiming at restoring (some) vision in these patients, different treatment strategies are being developed and/or already tested. These approaches include technological ones using electronic implants as well as biological ones, relying on genetic techniques.

Irrespective of the method and its specific issues, two fundamental biological challenges have to be addressed: The first challenge results from the fact that the retina “breaks down” the viewed scene into approx. 40 visual feature representations (“images”), each relayed to higher visual centres via parallel channels. This prompted the idea of making use of the existing (or remaining) retinal circuits and feeding in “artificial photoreceptor input” as upstream as possible – for instance, by stimulating bipolar cells (BCs), secondary neurons after the pho-toreceptors, electrically 8, with glutamate, or by rendering them light-sensitive. However, this creates yet another problem, because already at the level of the BCs, about 10-15 parallel signal channels exist, which need to be stimulated differentially (e.g. On vs. Off, transient vs. sustained, etc.) to drive the downstream network and provide the essential input to generate the “correct” retinal output. The second challenge lies in the fact that on the long run, retinal circuits need input to remain structurally and functionnally intact. In the photoreceptor degenerating retina, circuits that lack photoreceptor input are soon remodelled, leading to spontaneous and/or oscillatory activity. While some of this remodelling may be reversible, remodelling could impair channel-specific stimulation and, hence, “reusing” retinal circuits.

Here, we suggest a new approach for restoring useful vision that does not rely on biologically “correct” channel-specific stimulation and that is flexible enough to also account for retinal circuit remodelling.