Expression of cell surface transmembrane carbonic anhydrase genes CA9 and CA12 in the human eye: overexpression of CA12 (CAXII) in glaucoma
- S-Y Liao1,
- S Ivanov2,
- A Ivanova3,
- S Ghosh4,
- M A Cote5,
- K Keefe6,
- M Coca-Prados4,
- E J Stanbridge1,
- M I Lerman3
- 1Department of Microbiology and Molecular Genetics, College of Medicine, University of California at Irvine, CA, USA
- 2Intramural Research Support Program, Science Applications International Corporation, Frederick, MD, USA
- 3Laboratory of Immunobiology, National Cancer Institute at Frederick, MD, USA
- 4Department of Ophthalmology & Visual Science, Yale University, CT, USA
- 5Department of Pathology, College of Medicine, University of California at Irvine, CA, USA
- 6Ophthalmic Pathology, Navy Medical Center, San Diego, CA, USA
- Correspondence to: Dr S-Y Liao, Department of Microbiology and Molecular Genetics, College of Medicine, University of California at Irvine, CA 92697-4025, USA; or Dr M Lerman, Laboratory of Immunobiology, National Cancer Institute at Frederick, Frederick, MD 21701, USA;
- Accepted 22 December 2002
- Revised 21 December 2002
Purpose: Carbonic anhydrase enzymes (CAs) are universally involved in many fundamental physiological processes, including acid base regulation and fluid formation and movement. In glaucoma patients, CA inhibitors are very effective in lowering intraocular pressure by reducing the rate of aqueous humour secretion mediated by the CAs in the ciliary epithelium. In this work, we investigated the expression and tissue distribution of two recently discovered CA genes CA9 (CAIX) and CA12 (CAXII) in fetal, neonatal, and adult human eyes with and without glaucoma.
Methods: CAIX and CAXII expression in 16 normal and 10 glaucomatous eyes, and in cultured non-pigmented ciliary epithelial cells (NPE) from normal and glaucoma eye donors was assessed by immunostaining. In addition, northern blot hybridisation was performed to assess expression of CA4, CA9, and CA12 mRNA in cultured NPE cells from normal and glaucoma donors.
Results: CAXII was localised primarily to the NPE with its expression prominent during embryonic eye development but which decreased significantly in adults. CAIX expression in the NPE was very low. The epithelium of cornea and lens occasionally expressed both enzymes at low levels during development and in adult eye, and no expression was detected in the retina. The NPE from glaucoma eyes expressed higher levels of CAXII, but not CAIX, in comparison with normal eyes. This expression pattern was retained in cultured NPE cell lines. NPE cells from a glaucoma patient showed a five-fold increase in the CA12 mRNA level with no detectable expression of CA9 mRNA. Also, no expression of the CA4 gene encoding a GPI anchored plasma membrane protein was detected on these northern blots.
Conclusions: Transmembrane CAIX and CAXII enzymes are expressed in the ciliary cells and, thus, may be involved in aqueous humour production. CA12 may be a targeted gene in glaucoma.
- CA, carbonic anhydrase (Arabic numerals denote the gene and corresponding mRNA while the Latin numerals denote the protein products)
- NPE, non-pigmented epithelial (ciliary) cells
- GPI, glycosylphosphatidylinositol lipid anchor
- ACG, angle closure glaucoma