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Gene regulation, development and disease of the vertebrate retina.

      The Marsh-Armstrong laboratory studies molecular mechanisms involved in gene regulation, development and disease of the central nervous system, focusing principally on the retina. Most of our studies are carried out in frogs in order to perform experimental approaches that rely on high throughput transgenesis. Currently, there are three major areas of interest:

(1) Metamorphic remodeling of the nervous system: Studying metamorphic programs has enabled us to identify molecular pathways that are general to vertebrate neural development by virtue of their regulation by thyroid hormone in frogs. In one particular lineage, the generation of ipsilaterally projecting retinal ganglion cells, we are studying how these cells are generated from neural progenitor cells as well as the novel axon guidance mechanism that they use.

(2) Photoreceptor degeneration: We have developed several frog models of photoreceptor degeneration that are similar to mammalian models but that enable novel experimental approaches. We are using these models to explore the nature of rhodopsin mutations that cause retinitis pigmentosa and the molecular mechanisms by which rod photoreceptors degenerate. We are also using some of these lines in High Throughput Screening (HTS) assays looking for chemicals that prevent or slow photoreceptor degenerations.

(3) Glaucoma: We are one of four labs that are part of a collaborative project, “Catalyst for a Cure” that is dedicated to understanding the molecular mechanisms underlying the loss of retinal ganglion cells in glaucoma. Most of these studies involve a mouse model of glaucoma, the DBA/2J mouse, and involve interventions that aim to slow disease progression.