OPTOGENETIC RESTORATION OF LIGHT SENSITIVITY IN THE DEGENERATING RETINA

Retinitis pigmentosa (RP) is a group of inherited retinal degenerative diseases affecting approximately 1:4.000 people and is one of the leading causes of blindness in working-age adults. The condition primarily leads to the progressive loss of photoreceptor cells, while inner retinal neurons remain largely intact. Despite the identification of over 250 causative genes, the genetic complexity of RP has hindered effective therapeutic development. The rd10 mouse line provides a valuable model for investigating pathology observed in human patients and to explore potential treatments.
Our project aims to characterize the degree of blindness by measuring visual responses in the primary visual cortex (V1). Using wide-field intrinsic optical imaging of hemodynamic signals in longitudinal sessions, we track responses to stimuli of varying contrast and luminance combined with retinotopic mapping. We characterize the decline in response strength as well as potential spatial reorganization of the retinotopic maps of V1 and neighbouring higher visual areas. Altogether, our work characterizes how the progressive dysfunction of rod and cone photoreceptor function is reflected in visual cortical population activity over several months.
Following the establishment of the time course of retinal degeneration at cortical levels, the ultimate goal of our study is to evaluate the impact of various optogenetic tools expressed in the retina on the attenuation of the progression of RP.
Acknowledgement: This work is financially supported by the Deutsche Forschungsgemeinschaft (DFG), Project number 492434978 - GRK 2862/1, Subprojects 9 and 10, I.S. and D.J. and by the DAAD under the Graduate School Scholarship Programme (GSSP).