Abstract
Purpose :
Visual pathways that signal luminance increments (ON pathway) and decrements (OFF pathway) have been suggested to differentially influence myopia progression and are more weakly driven by defocused stimuli. However, inner retinal signals (including those from ON and OFF pathways) have not been directly studied electrophysiologically in myopic eyes. Here, we investigate how responses from single inner retinal neurons are modulated in myopia.
Methods :
Lens-induced myopia (LIM) in C57BL/6J mice was generated unilaterally by placing a -10D lens over the OD eye, leaving the OS eye as a contralateral control (LIM, n=29). Refractive errors (RE) were measured in animals before lens placement and at the end of the treatment period (>2 weeks). A subset of mice were left untreated as naïve controls (Ctrl, n=9). Retinas were collected and prepared for whole-cell voltage clamp recordings. A white OLED screen (max luminance: ~2,000 cd/m2) was used to generate full-field, 500 ms duration flash stimuli. Light-evoked ON and OFF excitatory and inhibitory responses were measured from single dark-adapted bipolar (BC) and amacrine cells (AC), identified via fluorescent labeling.
Results :
All LIM mice developed a myopic shift (ΔRE OD - OS) after 2 weeks (-2.7±0.2 D, p<0.001) whereas Ctrl mice did not. The average ON and OFF excitatory response across all recorded cells was ~50% weaker in myopic (n=14 cells) than non-myopic eyes (Ctrl + LIM OS eyes, n=12 cells; p=0.034). Interestingly, myopia affected ON- and OFF-driven inhibition in opposite directions. Combining all recorded cells, ON inhibition decreased ~28% and OFF inhibition increased ~42% in myopic (ON n=23, OFF n=20 cells) compared to non-myopic eyes (ON n=14, OFF n=12 cells; p<0.001). In myopic eyes, ACs, cone BCs, and rod BCs primarily contributed to reduced ON inhibition while ACs and OFF cone BCs primarily contributed to increased OFF inhibition.
Conclusions :
Our results provide direct electrophysiological evidence suggesting modulation of inner retinal ON and OFF responses in myopic eyes. On average, LIM led to weaker ON and OFF excitatory drive, weaker ON-driven inhibition, and stronger OFF-driven inhibition to inner retinal neurons. Our preliminary findings suggest that retinal dysfunction in myopia includes altered ON/OFF retinal balance and supports our ongoing investigation of the effects of myopia on visual signaling in all retinal cell types.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.