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David J Calkins; Of axons and dendrites: drivers of progression in glaucoma. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Presentation Description :
Glaucoma targets retinal ganglion cell neurons and their axons, which form the optic projection to the brain. The disease is associated with both aging and sensitivity to intraocular pressure (IOP). These factors compound in complex ways to convey diverse biochemical, biomechanical and bioenergetic stress to the ganglion cell. This is so especially for the unmyelinated axon segment as it passes through the nerve head. Nevertheless degeneration evolves bidirectionally. Pathogenesis involves a distal program that affects the axonal projection to the brain and a proximal program that affects ganglion cell dendrites, synapses and cell bodies in the retina. Progression follows a particular spatial pattern, with loss of both function and structure filling in from one retinotopic sector to the next. Our goal is to understand how sectorial progression reflects critical mechanisms of pathogenesis and how these mechanisms differ between proximal and distal degeneration. This presentation will focus on our progress towards this goal, through emerging physiological, pharmacological and anatomical results from our laboratory and collaborations. Collectively, these studies suggest that both distal and proximal programs are highly dynamic with possible cross-talk between axonal and dendritic compartments. Evidence from chronic and inducible models suggests a level of remodeling and adaptation in the ganglion cell projection that counters the view of a unidirectional push towards tissue loss. This adaptive response may serve to isolate glaucomatous injury and conserve functon and may present opportunities for new therapeutic interventions.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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