Abstract
Purpose :
Bright ambient environments, which are signaled by retinal cone pathways, are strongly protective against myopia progression. Recently, dim conditions, which are signaled by rod pathways, were found to attenuate myopia in mice, and functional rod pathways are critical for myopia development. Yet, rod pathway signals have not been directly studied in myopic eyes. Here, we use a single-cell approach to investigate how rod pathway signaling is modulated in a mouse model of lens-induced myopia (LIM).
Methods :
Myopia in C57BL/6J mice (males, P28) was generated by fixing a -10 diopter (D) lens over the right eye (OD) leaving the left eye (OS) free (n=12). A subset of mice was not treated with lenses (n=3). Refractive error was measured before lens placement and weekly for at least two weeks. After lens treatment, retinas were prepared for single-cell voltage clamp recordings. White, full-field, flash stimuli (0.003 – 300 cd/m2, 500 msec duration) were presented to dark-adapted rod bipolar cells (RBCs) identified via fluorescent labeling. Light-evoked inhibitory responses were compared between LIM (n=9 cells) and non-LIM (LIM OS + untreated, n=8 cells) eyes.
Results :
After two weeks, LIM mice developed a myopic shift (OD – OS, -5.5±0.6 D, p<0.001, ANOVA) while untreated mice did not. We found that RBC response peak amplitude and latency (time-to-peak) were significantly modulated by lens treatment across flash intensity (interaction effects, peak amplitude: p=0.007, latency: p=0.022, ANOVAs). When responses were binned across flash intensities and compared to non-LIM responses, LIM response peak amplitudes were ~25% weaker with scotopic flashes (6.4±1.4 vs. 8.5±1.6 pA, p=0.32) but ~39% stronger with photopic flashes (15.7±2.3 vs. 11.3±2.1 pA, p=0.09), though they were not individually significant. Moreover, while response latency in LIM eyes was delayed across flash intensities, it was most pronounced with scotopic flashes (383±18 vs. 263±27 ms, p<0.001).
Conclusions :
Our results provide direct electrophysiological evidence showing rod pathway signal strength and timing are altered in myopia. Interestingly, the direction of change was a function of stimulus intensity (reduced with scotopic stimuli but increased with photopic stimuli). Our preliminary findings suggest myopia affects rod pathway signal balance which may play a role in initiating or progressing myopic eye growth.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.