June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Single-cell recordings reveal modulation of ON and OFF retinal signals in the myopic murine eye
Author Affiliations & Notes
  • Reece Mazade
    Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
    Atlanta VA Center for Visual & Neurocognitive Rehabilitation, Decatur, Georgia, United States
  • Machelle T Pardue
    Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
    Atlanta VA Center for Visual & Neurocognitive Rehabilitation, Decatur, Georgia, United States
  • Footnotes
    Commercial Relationships   Reece Mazade None; Machelle Pardue None
  • Footnotes
    Support  NIH R01 EY016435 (MTP) and Dept. of Veterans Affairs Research Career Scientist Award RX003134 (MTP)
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4580 – F0442. doi:
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    • Get Citation

      Reece Mazade, Machelle T Pardue; Single-cell recordings reveal modulation of ON and OFF retinal signals in the myopic murine eye. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4580 – F0442.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

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