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Carbonic anhydrase gene 12 is overexpressed in glaucoma

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Investigators in California and Maryland examined 16 normal (including fetal and neonatal) eyes and 10 glaucomatous eyes for the presence of various cell surface transmembrane carbonic anhydrase genes (CA). Normal developing eyes expressed CAIX and CAXII enzyme proteins in ciliary, corneal, and lens epithelia as well as the endothelium. After birth, the intensity of CAXII immunoreactivity decreased and was no longer expressed in the inner membrane of the retina. Levels fell further in adult eyes. In particular CAIX was not expressed in the ciliary epithelium although it had been very weakly expressed in developing eyes.

In glaucoma, positive immunoreactivity of both genes was weak but a striking finding was high levels of CAXII but absent CAIX expression in the non-pigmented ciliary epithelium (NPE). These patterns of expression were maintained in cultured NPE cells.

The authors conclude that CAIX and CAXII probably play an important role in aqueous humour production. Thus, the silencing of the CA9 gene in adult eyes could lead to overexpression of CA12 in NPE cells, with consequent overproduction of aqueous humour, high intraocular pressure and, hence, glaucoma.

The implications are that investigating CA12 could provide a framework to better understand fluid equilibrium in the eye; and it might impact upon the development of more selective topical inhibitors of CAXII in treatment.

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