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. Many of our studies are carried out in frogs in order to perform experimental approaches that rely on high throughput transgenesis. Currently, there are four 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. We are studying a class of enzymes, deiodinase enzymes, which are critical for regulating post-embryonic neurogenesis. By studying genes controlled by thyroid hormone in neural progenitors, we study molecular pathways involved in the regulation of vertebrate post-embryonic neurogenesis. 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 also plan to use these models to screen for therapeutic interventions that aim to prevent or slow photoreceptor degenerations, particularly of cone photoreceptors.(3) Glaucoma: We are one of four labs that are part of a collaborative project, ìCatalyst for a Cureî that is dedicated to understanding the mechanisms by which retinal ganglion cells die in glaucoma as well as identifying potential therapeutic interventions. The other laboratories involved in the CFC collaborative are those of Monica Vetter (U. Utah), Phil Horner (U. Washington), and David Calkins (Vanderbilt U.). Most of these studies involve a mouse model of glaucoma, the DBA/2J mouse.