Morphological and Physiological Characteristics of Ganglion Cells in P23H Rat Retina

Abstract

Purpose: : Retinal prosthesis provides a promising approach to restore vision following the photoreceptor loss in people affected by retinitis pigmentosa or macula degeneration. The concept has already been validated in patients, but the physiological state of the surviving cells and network remains partially unknown. We therefore examined retinal ganglion cells (RGCs) at physiological and morphological levels in P23H rats at different ages during and after photoreceptor degeneration.

Methods: : Whole cell patch clamp recordings were obtained by RGCs of P23H rats and compared to age-matched (10-18 weeks) control Sprague Dawley rats. Immunostaining techniques were used to test the presence of morphological alterations.

Results: : Whole cell patch clamp recordings showed that in P23H rats, RGCs, although still able to fire action potentials, are significantly depolarized compared to control animals. Resting potential was 39.23 + 8.97 mV (N=13) compared to 63.06 + 7.07 mV in control rats (N=20). (P<0.0001, unpaired two tailed t-test.). In rats older than 100 days, mini Post Synaptic Currents amplitude was very much reduced in P23H ganglion cells compared to control animals and the excitatory input seemed to be the first one to be affected (7/15).RGCs were immunolabelled with the BRN3A antibody to determine if photoreceptor loss lead to secondary degeneration of RGCs in P23H rats as it has been seen in patients. In P23H rat retina at 11-14 months, the RGCs number was decreased by 39.0 % with respect to age-matched control animals.

Conclusions: : Our neuroanatomical results provide clear evidence for a progressive RGCs degeneration after photoreceptor loss in P23H rats as already seen in people affected by retinitis pigmentosa. Patch clamp recordings revealed that at advanced degeneration stages, RGCs are still capable of generating action potentials but that they receive much less inputs from the upstream network, in particular from the off pathway. These differences with control animals have to be kept in mind when designing electronic devices which need to stimulate a retina where the network characteristics have changed.

Keywords: ganglion cells • retinal degenerations: cell biology • electrophysiology: non-clinical