Abstract
Purpose :
Microelectronic retinal prostheses have been implanted to restore the vision of individuals blinded by outer retinal degenerative diseases but showed considerable performance variations across users. Given that retinitis pigmentosa has the numerous genotypes which have distinct phenotypes, there is a possibility of different characteristics in electrically-evoked responses across those genotypes. However, the past prosthetic researches have typically used retinal degeneration 1 (rd1) and 10 (rd10) models which have Pde6b gene mutation. To extend our understanding to another type of degenerate retinas, we studied electric responses of retinal ganglion cells (RGCs) in rd8 mice which have Crb1 gene mutation for the first time.
Methods :
We used cell-attached patch clamping method to record spikes from RGCs in the wild-type (wt, C57BL/6J; n = 6 and n = 7 for ON and OFF RGCs, respectively) and rd8 mice (C57BL/6N; n = 7 and n = 9 for ON and OFF RGCs, respectively). First, ON and OFF RGCs were identified by their responses to 1-sec-long stationary white spot flash on a gray background. Second, an electric stimulus (4 ms duration, -100 μA) was applied to evoke network-mediated responses. Similar to our previous works, the electrically-elicited spiking responses were divided into two parts: first burst and delayed response.
Results :
Both peak firing rate and spike count of delayed responses arising in rd8 RGCs were considerably lower compared to those of wt RGCs. For example, in the wt mice, the peak firing rates of ON and OFF RGCs were 277.4±122.4 and 361.5±209.5 Hz; however, those were decreased in the rd8 mice to 162.7±149.4 and 260.1±177.3 Hz, respectively. Also, the average spike counts of both ON and OFF types were smaller in rd8 than wt: 49.1±26.3 vs. 17.1±13.4 (wt vs. rd8 for ON RGCs), and 12.2±9.6 vs. 8.3±4.4 (wt vs. rd8 for OFF RGCs), respectively.
Conclusions :
In summary, we characterized the electrically-evoked responses of ON and OFF RGCs in rd8 mice. In addition to our recent publication regarding network-mediated responses of rd10 mice, systematic comparison of results from rd8 vs. rd10 will enhance our understanding of electrically-elicited responses of RGCs in different forms of retinal degeneration. These researches are likely to contribute in reduction of performance variations across prosthetic users.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.