Abstract
Purpose: :
This work is related to the efforts of the Boston Retinal Implant Project to develop a subretinal prosthesis to restore vision to the blind. The specific purpose of this study was to compare the thresholds and response properties of retinal ganglion cells (RGCs) in wild-type and rd1 mice to electrical stimulation of the retinal neural network.
Methods: :
Extracellularly recorded responses were obtained from RGCs in isolated retinas from rd1 (C3H/HeJ) and wild-type (C57BL/6) mice. Retinas were stimulated with biphasic current pulses applied to the outer retinal surface with a 400-µm diameter electrode.
Results: :
Three types of electrically evoked responses were observed in both wild-type and rd1 RGCs. Type I cells elicited a single burst of spikes within 20 ms following application of the electrical stimulus, type II cells elicited a single burst of spikes with a latency greater than 37 ms following the electrical stimulus, and type III cells elicited two and occasionally three bursts of spikes. All three types were sensitive to bath-applied glutamate receptor antagonists, indicating that the RGCs were stimulated through activation of the neural network.For all ages examined, ranging from postnatal day (P) 25 to P186, the stimulation thresholds of the RGCs were overall consistently higher in rd1 mice. In wild-type mice, the thresholds ranged from 4.2 - 60 µA, with a median value of 14 µA (n = 43). In rd1 mice, the thresholds ranged from 22 - 100 µA, with a median value of 50 µA (n = 50).
Conclusions: :
The responses of RGCs to biphasic current pulses were similar in both wild-type and rd1 mouse retinas. Overall, the stimulation thresholds of wild-type and rd1 RGCs to the biphasic current pulses were 3.6-fold higher in rd1 mouse retinas. We propose that the elevated thresholds are due to loss of photoreceptors rather than secondary changes that may occur in the inner retina.
Keywords: ganglion cells • degenerations/dystrophies • retina