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Editors Selection IGR 16-3

Basic Research: Best2 and reduced IOP

Terete Borras

Comment by Terete Borras on:

25849 Bestrophin 2 is expressed in human non-pigmented ciliary epithelium but not retinal pigment epithelium, Zhang Y; Patil RV; Marmorstein AD, Molecular Vision, 2010; 16: 200-206


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Bestrophin 2, or Best2, is a calcium-activated chloride channel which appears to also exhibit other functions. Although another member of the Bestrophin family, Best1, has been linked to the development of several retinopathies, Best2 has not been associated with any disease. A recent paper by Zhang et al. (IGR 12-2: 625) shows that the Best2 gene is expressed in the human non-pigmented ciliary epithelium. Using transgenic animals with a Best2-disrupted LacZ transgene, this report is the continuation of a thorough mouse study by the same group in which RT-PCR and immunohistochemistry shows Best2 expression in the mouse non-pigmented ciliary epithelium. In this study, the Best2 null mouse was also found to have reduced IOP. Because of the location of Best2 expression to the aqueous humor formation tissue, the authors inferred there that the potential cause of lower IOP was a reduction in aqueous humor production, though aqueous fluid inflow or outflow were not measured.

The tissue specificity of expression of any gene is pretty wellconserved across species. Thus, although it is always important to confirm the tissue expression from mouse to human, the results of the present study are pretty much expected. It was not surprising that Bst2 was expressed in the human NPE. But, while the mouse study was extensive, the current human paper is very short, comprising just the characterization of a new anti-hBest2 antibody and limited immunohistochemistry of human specimens. A more developed work, taking into account information on more individual specimens and, specially, measurements of the effect of silencing Best2 on human outflow facility would have been desirable. As the authors had previously proposed, targeting reduction of Best2 expression in the NPE could potentially be a new strategy for glaucoma treatment. Most likely, this laboratory would be able to extend these studies and provide such validation in the future.



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