Bestrophin-2 Protein And Glaucoma

Alan Marmorstein, PhD
University of Arizona (Tucson, AZ)
Year Awarded:
2009
Grant Duration:
April 1, 2009 to March 31, 2011
Disease:
Glaucoma
Award Amount:
$100,000
Grant Reference ID:
G2009010
Award Type:
Standard
Award Region:
US Southwestern
Recipient of the Thomas R. Lee award for National Glaucoma Research
Alan Marmorstein, PhD

Bestrophin-2 And Aqueous Humor Dynamics

Summary

This study seeks to determine how the Bestrophin-2 protein controls the flow of the fluid in the eye, the aqueous humor.

Details

We have recently identified the Bestrophin-2 protein (Best2) as a key regulator of fluid dynamics in the eye. This study will determine, via two specific aims, the mechanisms underlying this unique activity. If successful, this study will lead to new therapeutic options for treatment of glaucoma. Specific aims are 1. To determine how Best2 functions to antagonize the formation of aqueous humor, the fluid found in the eye. 2. To determine how absence of Best2 enhances outflow of aqueous humor from the eye.

Research Updates

The goal of this study is to understand the role of bestrophin-2 (Best2) in regulating aqueous flow and drainage. To accomplish this, we have proposed two specific aims. The first was to determine how Best2 functions to antagonize the formation of aqueous humor. To this end, we have examined the distribution of Best2 in human eyes and found that, like in mice, Best2 is only expressed in the basal plasma membrane of non-pigmented epithelial (NPE) cells. NPE are cells of the ciliary body, a ring of tissue that encircles the lens that both controls its movement through tiny muscles and controls the passage of fluid between the front and back of the eye.

A more significant finding however, is that Best2 physiologically carries a bicarbonate conductance in certain cells and that this conductance is absent in mice deficient in Best2. A bicarbonate conductance is an electrical signal that's produced in cells by the movement of the bicarbonate chemical across a cell membrane, allowing cells to communicate with each other. This strongly suggests that Best2 functions to carry a bicarbonate conductance in the NPE as well. This indicates that the entire bestrophin family of proteins may be involved in regulating bicarbonate transport.

Our second specific aim was to determine how absence of Best2 enhances outflow. We are currently examining levels of bioactive peptides in order to meet the goals of this aim.

Publications

Zhang, Y.,. R. V. Patil, and A. D. Marmorstein. Bestrophin 2 is expressed in the human non-pigmented ciliary epithelium but not retinal pigment epithelium -Molecular Vision.  

(This report establishes that Best2 is expressed on the basal surface of NPE cells in man) Yu K, R. Lujan, A. D. Marmorstein, S. Gabriel, and H. C. Hartzell. Bestrophin 2 mediates bicarbonate transport by goblet cells in mammalian colon. - In Press (Journal of Clinical Investigation) [PMID:nd][link not available] (This report establishes that Best2 carries a physiologically important bicarbonate conductance in colon.)
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