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Steven F Stasheff, Erik Nylen, Eric Hassey; Retinal ganglion cell stimulus-response relationships identify pathway-specific alterations for categorization and staging of retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4831.
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© ARVO (1962-2015); The Authors (2016-present)
We present a method for characterizing retinal ganglion cell (RGC) stimulus-response (S-R) relationships to distinguish specific subclasses of ON & OFF responding RGCs, and identify specific shifts in sensitivity, gain, and dynamic range that may occur in certain subclasses during retinal degeneration. The objective is to reveal alterations in select signal processing pathways of the retina specific to various forms of retinal degeneration at intermediate stages.
Building upon previous findings in mature wild-type (wt) mice (Volgyi et al, J Neurosci 2004), we used in vitro multielectrode recording to sample ON and OFF responses of individual RGCs to stimuli of various intensities. Extracellular action potentials were recorded simultaneously from 30-90 retinal ganglion cells in the retina of 14 day old wt and rd1 mice. Full field light flashes were presented at 17 intensities (0-34 µW/cm2·s, 1 sec) in randomized order, and for each RGC the number of spikes during the 1 sec following flash on- or offset was plotted vs. stimulus intensity. Each plot was fit to a Michaelis-Menten relationship using Matlab’s Curve-fitting Toolbox, and RGC responses were classified into several types according to parameters extracted from the best fit S-R curves for all cells in each strain.
In both wt and rd1 mice, ON cells segregate into three and OFF cells into four groups, comparable to mature RGCs (Volgyi et al). For most response groups, rd1 curves were right-shifted parallel to wt curves, but high-sensitivity ON and OFF rd1 cells had decreased slope (gain) relative to wt, whereas low-sensitivity OFF rd1 cells had a more markedly elevated threshold and steeper slope (gain). This pattern suggests differential changes in rod vs. cone input to ON and OFF pathways.
Shifts in the parameters of RGC S-R curves occur as degeneration progresses in the rd1 mouse. The nature and degree of these changes are distinguishable among subgroups of RGCs. This indicates changes in specific visual processing pathways that may be distinctive signatures for particular forms of retinal degeneration, and our approach may direct more detailed evaluation of these pathways. We are investigating characteristic shifts in S-R curves in other mouse models of retinal degeneration. Ultimately, this method may help diagnose and stage patients with blinding diseases.
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