Understanding the role of the Trabecular Meshwork in pressure regulation

Jeffrey Marchant, PhD
Tufts University School of Medicine (Boston, MA)
Year Awarded:
2006
Grant Duration:
April 1, 2006 to March 31, 2009
Disease:
Glaucoma
Award Amount:
$90,000
Grant Reference ID:
G2006011
Award Type:
Standard
Award Region:
US Northeastern

Matrix Interactions Pertinent to High IOP and Glaucoma

Summary

This study will evaluate the effect of altering trabecular meshwork components on TM function and regulation of intraocular pressure.

Details


Elevated intraocular pressure (IOP) is a major risk factor for glaucoma and results from alteration of the pathway that drains aqueous humor from the anterior eye. While studies have been performed to characterize this pathway in human and non-human primate tissues, our understanding of its organization is still very limited. The outflow pathway is comprised, in part, of a region known as the trabecular meshwork (TM). The TM is a series of cells and connective tissues organized as a filter. Alterations in several TM components have been correlated with elevated IOP. We have identified a new component in the TM that we hypothesize will stabilize this region and help to regulate normal IOP. We will examine the TM in the mouse to evaluate the organization of this and other components thought to regulate IOP. We will then exploit the genetic capabilities of the mouse and examine mutants that have altered expression of key TM regulatory components. We will evaluate the affect these alterations have on TM function and IOP regulation. Given the similarities between the components in mouse and human TM tissues, our findings will likely be highly relevant to human IOP regulation and thus may lead to intervention strategies for the future.

Publications

Gould, D.B., Marchant, J.K., Savinova, O., Smith, R.S., John, S.W.M. (2007) Col4a1 mutation causes endoplasmic reticulum stress and genetically modifiable ocular dysgenesis. Hum. Mol. Genetics 16(7): 798-807.  

Howell, G.R., Marchant, J.K., John, S.W.M. (2008) Mouse Models: A key system for revolutionizing understanding of glaucoma, In Eye, Retina, and Visual System of the Mouse, Leo M. Chalupa and Robert W. Williams, Editors, University of California, Davis and University of Tennessee Medical School, Chapter 3, pp479-491 MIT Press. [book chapter]
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