RPE Cell Volume Regulation by Bestrophins
Principal Investigator
Project Summary
There are a number of inherited forms of macular degeneration which may provide insight into age-related macular degeneration. One inherited form of macular degeneration is caused by a gene (bestrophin) that makes a protein that is a chloride ion channel. Chloride ion channels are conduits for movement of chloride ions between the inside and outside of the cell. Although it is not understood how the dysfunction of a chloride ion channel can cause macular degeneration, Dr. Hartzell plans to use genetic models to explore the role that chloride channels play in the function of the retina. Dr. Hartzell believes that the function of these channels may be to regulate the volume of the cell. This is important because a lack of volume regulation causes cells to burst.
Publications
Hartzell C, Qu Z, Putzier I, Artinian L, Chien LT, Cui Y. Looking chloride channels straight in the eye: bestrophins, lipofuscinosis, and retinal degeneration. Physiology 20, 292-302 (2005). 
Qu, Z., Y. Cui, C. Hartzell. A short motif in the C-terminus of mouse bestrophin-4 inhibits its activation as a Cl channel. FEBS Lett. 580, 2141-2146 (2006).
Qu, Z., Chien, L-T., Cui, Y., and H. C. Hartzell. The anion-selective pore of the bestrophins, a family of chloride channels associated with retinal degeneration. Journal of Neuroscience 26, 5411 - 5419 (2006).
Yu, K., Y.Y. Cui, and H. C. Hartzell. The Bestrophin Mutation A243V Linked to Adult-Onset Vitelliform Macular Dystrophy Impairs Its Chloride Channel Function. Investigative Ophthalmology and Visual Sciences 49, 56 - 61 (2006).
Chien, L.T., and H. C. Hartzell. Drosophila Bestrophin-1 Chloride Current Is Dually Regulated by Calcium and Cell Volume. J. Gen. Physiol. 130, 513-534 (2007).
Hartzell, H.C., Z. Qu, K. Yu, Q. Xiao, L.T. Chien. Molecular Physiology of Bestrophins: A Family of Multi-functional Chloride Channels Linked to Macular Degeneration. Physiological Reviews 88: 639-672 (2008).
Bakall, B., P. McLaughlin, J.B. Stanton, H.C. Hartzell, L.Y. Marmorstein, and A.D. Marmorstein. Bestrophin-2 is involved in the generation of intraocular pressure. Invest. Ophthalmol. Vis. Sci. 49: 1563-1570 (2008).
First published on: June 11, 2008
Last modified on: May 06, 2024