June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Characterization of cone membrane physiology during secondary cone degeneration in the rd10 model of retinitis pigmentosa
Author Affiliations & Notes
  • Erika Ellis
    Ophthalmology, Jules Stein Eye Institute, Los Angeles, California, United States
  • Gordon Fain
    Ophthalmology, Jules Stein Eye Institute, Los Angeles, California, United States
  • AP Sampath
    Ophthalmology, Jules Stein Eye Institute, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Erika Ellis None; Gordon Fain None; AP Sampath None
  • Footnotes
    Support  This research was funded by the following grants: National Institutes of Health EY001844 to G.L. Fain; National Institutes of Health EY027193 to AP Sampath; Research to Prevent Blindness USA unrestricted grant to the UCLA Department of Ophthalmology; and National Eye Institute Core Grant EY00311 to the Jules Stein Eye Institute
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2693. doi:
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    • Get Citation

      Erika Ellis, Gordon Fain, AP Sampath; Characterization of cone membrane physiology during secondary cone degeneration in the rd10 model of retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2693.

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

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Abstract

Purpose : In retinitis pigmentosa, secondary degeneration of cones is one of the most debilitating features of the disease. Currently there is little known about how cone membrane physiology changes during secondary cone degeneration. In this study, we sought to characterize cone membrane physiology throughout secondary cone degeneration.

Methods : Using the rd10 mouse model of retinitis pigmentosa, we performed whole-cell patch-clamp recordings from cones in retinal slices. We measured passive membrane properties, recorded light-evoked responses, and measured isolated conductances using voltage-clamp protocols in combination with specific channel-blocking agents. During patch-clamp recordings, cells were filled with a fluorescent dye and cell morphology was imaged after recordings were completed. Experiments were performed in rd10 animals between 3- and 9-weeks old.

Results : Cones in the rd10 mouse showed significantly altered morphology even at the earliest time point, with no outer segment seen on any cells. In line with this, cone membrane capacitance was significantly lower than normal even at the earliest time point and showed no significant change over 9 weeks, with an average membrane capacitance of 2.2pF (n=44). Even at late time points, small light-evoked responses could be elicited from most cones with a bright flash from a 405nm LED. The cone resting membrane potential showed no significant change during degeneration, with an average resting membrane potential of -50mV (n=34), similar to WT cones. Cones maintained a robust HCN1 conductance at all time points. Preliminary recordings of synaptic calcium currents suggest a decrease in the calcium current with age.

Conclusions : Our results show that degenerating cones maintain a depolarized resting membrane potential, even after the loss of the outer segment. The presence of light-evoked responses, although small and desensitized, suggests that cones can maintain ectopic expression of cyclic-nucleotide-gated channels, which with other conductances still present in the membrane may be responsible for maintaining the cell in a depolarized state. There seems to be little change in the HCN1 conductance, but voltage-gated calcium currents appear to be diminished as degeneration progresses.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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