HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bakall, B. Articles by Marmorstein, A. D. Search for Related Content PubMed PubMed Citation Articles by Bakall, B. Articles by Marmorstein, A. D.

Bestrophin-2 Is Involved in the Generation of Intraocular Pressure

¹From the Departments of Ophthalmology and Vision Science and ³Physiology, and the ⁴College of Optical Sciences, University of Arizona, Tucson, Arizona; and the ²Department of Cell Biology, Emory University, Atlanta, Georgia.

PURPOSE. The bestrophin family of proteins has been demonstrated to generate or regulate Ca²⁺-activated Cl^– conductances. Mutations in bestrophin-1 (Best1) cause several blinding eye diseases, but little is known about other bestrophin family members. This study involved disruption of the Best2 gene in mice.

METHODS. The mouse Best2 gene was disrupted by replacing exons 1, 2, and part of exon 3 with a Lac Z. The expression profile of Bestrophin-2 (Best2) was examined using RT-PCR, X-gal staining, and immunohistochemistry. Intraocular pressure (IOP) was measured by anterior chamber cannulation.

RESULTS. RT-PCR of mouse tissues revealed Best2 mRNA in eye, colon, nasal epithelia, trachea, brain, lung, and kidney. X-gal staining, confirmed expression in colon epithelia and in the eye, in the nonpigmented epithelia (NPE). Best2 was not expressed in RPE cells. Best2 protein was observed only in NPE and colon epithelia. The absence of Best2 had no obvious deleterious effect on the mice. However, the Best2^–/– mice were found to have significantly (P < 0.02) diminished IOP with respect to the Best2^+/+ and Best2^+/– littermates. The Best2^–/– and Best2^+/– mice responded better to the carbonic anhydrase inhibitor brinzolamide than did their Best2^+/+ littermates, although the β-blocker timolol brought IOP to the same level, regardless of genotype.

CONCLUSIONS. Best2 plays a role in the generation of IOP by regulating formation of aqueous humor, and inhibition of Best2 function represents an attractive new avenue for regulating IOP in individuals with glaucoma.

This article has been cited by other articles:

				S. J. Kleene The Electrochemical Basis of Odor Transduction in Vertebrate Olfactory Cilia Chem Senses, August 14, 2008; (2008) bjn048v1. [Abstract] [Full Text] [PDF]