Retinal circuits in degenerative disease
Basic physiology of the degenerating retina — how circuits remodel, what remains intact, and what any restorative therapy must respect.
Every restorative therapy for retinal degeneration — gene replacement, optogenetics, photoswitches, cell transplantation, neuroprotection — acts on a retina that has already been remodeled by disease. Bipolar cell dendrites retract, ganglion cell receptive fields reorganize, glial scaffolding changes. Designing therapies that work in patients (not just in early-stage models) requires a clear-eyed understanding of those changes.
This program uses ex vivo and in vivo electrophysiology — whole-cell patch clamp, multi-electrode arrays, and ERG — in animal models of inherited and age-related retinal degeneration. Open questions include:
- Which classes of inner retinal neurons retain functional output, and at what disease stage does that change?
- How do excitatory and inhibitory inputs to ganglion cells reorganize as photoreceptor input is lost?
- What are the practical signal-to-noise limits for detecting therapeutic rescue, given the spontaneous oscillatory activity that emerges in the deafferented inner retina?
The work informs the photoswitch program directly — it tells us which cells are good targets and which response patterns to expect — and it stands on its own as a contribution to the basic science of retinal degeneration.
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