Carbonic anhydrase IX (CAIX) is a transmembrane protein that is specifically overexpressed on the surface of hypoxic tumor cells. With the function of regulating the acidity of tumor cells both inside and outside, CAIX is closely related to tumor proliferation, invasion and metastasis. Therefore, CAIX is a promising target for tumor imaging and therapy. Herein, we summarized recent advances in CAIX-based tumor imaging, therapy and theranostics, and prospected future applications of using CAIX as an anti-tumor target.
Carbonic Anhydrase IX ; Carbonic Anhydrases/metabolism* ; Cell Line, Tumor

PURPOSE: To evaluate the morphological changes in Muller cells of an induced diabetic rat model with carbonic anhydrase histochemical staining. METHODS: Retinae of three normal rats and four streptozotocin-induced diabetic rats were used. The morphological changes in the Muller cells of these retinae were observed using enzyme histochemical staining. RESULTS: The numbers of positive staining Muller cells in diabetic rats retinae were significantly lower than those of the normal rats. In addition, the shape of the Muller cell bodies in the streptozotocin-induced diabetic rat model's retina changed from polygonal to abnormally flat. Furthermore, the staining of the Muller cells' segment in the outer nuclear layer of the diabetic rat's retinae were weaker, and some Muller cell segments were not stained at all. CONCLUSIONS: The numbers of Muller cells in diabetic rats' retinae were significantly lower than those of the normal rats. In addition, the features of Muller cell bodies of the diabetic rats were changed morphologically.
Animals ; Carbonic Anhydrases ; Ependymoglial Cells* ; Models, Animal ; Rats* ; Retina*

The purpose of this study was to investigate the effect of 2% dorzolamide, a topical carbonic anhydrase inhibitor, on corneal endothelium. Corneal endothelial permeability, central corneal thickness, central corneal endothelial cell density and intraocular pressure were measured in both eyes before(baseline) and after the use of 2% dorzolamide t.i.d. in one eye for one week. There was significant decrease in intraocular pressure(p=0.04) after the use of 2% dorzolamide t.i.d. for one week, but there were no significant changes in corneal endothelial permeability, central corneal thickness and central corneal endothelial cell density(p>0.05 in all).
Carbonic Anhydrases ; Endothelial Cells ; Endothelium, Corneal* ; Intraocular Pressure ; Permeability

The increasing atmospheric carbon dioxide levels have been correlated with global warming. Carbonic anhydrases (CA) are the fastest among the known enzymes to improve carbon capture. The capture of carbon dioxide needs high temperature and alkaline condition, which is necessary for CaCO₃ precipitation in the mineralization process. In order to use CAs for biomimetic carbon sequestration, thermo-alkali-stable CAs are, therefore, essential, and polyextremophilic microbes are one of the important sources of these enzymes. The current review focuses on both those isolated by thermophilic organisms from the extreme environments and those obtained by protein engineering techniques, and the industrial application of the immobilized CAs is also briefly addressed. To reduce the greenhouse effect and delay global warming, we think further research efforts should be devoted to broadening the scope of searching for carbonic anhydrase, modifying the technology of protein engineering and developing highly efficient immobilization strategies.
Biomimetics ; Carbon Dioxide ; Carbon Sequestration ; Carbonic Anhydrases ; Protein Engineering

PURPOSE: To investigate and compare the effects of topical carbonic anhydrase inhibitors on the production and expression of nitric oxide in cultured human trabecular meshwork cells (HTMC). METHODS: Primarily cultured HTMC were exposed to 0, 10, and 100 microM dorzolamide and brinzolamide using serum-deprived media for 3 days. Production of nitric oxide was assessed with Griess assay. Expressions of eNOS mRNA were assessed with RT-PCR. RESULTS: Both dorzolamide and brinzolamide increased the production of nitric oxide eNOS activity (p < 0.05). Dorzolamide had a more potent effect than brinzolamide on the production of nitric oxide and the expression of eNOS mRNA. CONCLUSIONS: Topical carbonic anhydrase inhibitors increased the production of nitric oxide, which was accompanied by increased eNOS activity. Dorzolamide had a more potent effect than brinzolamide on the production of nitric oxide and expression of eNOS mRNA in HTMC. The increased production of nitric oxide by topical carbonic anhydrase inhibitors involves mechanisms other than carbonic anhydrase inhibition.
Carbon* ; Carbonic Anhydrase Inhibitors* ; Carbonic Anhydrases* ; Humans ; Nitric Oxide* ; RNA, Messenger ; Trabecular Meshwork*

A number of acid-base or electrolyte disorders are associated with decreased or increased HCO3- reabsorption in the renal tubules. The present study was to examine the alterations of expression and distribution of Carbonic anhydrase II in the kidneys of normal and potassium-depleted rats using Western blot analysis and immuno-histochemistry. Western blot analysis demonstrated that CA II protein, ~30 kDa at molecular mass, was abundantly expressed in normal group. All potassium-depleted groups showed slightly increased CA II protein compared to normal group. In control group, immunoreactivity of CA II protein was detected in the entire collecting duct. Signal intensity was prominent in the intercalated cells and weak in the principal cells of the cortical collecting ducts. In potassium-depleted groups, the pattern of cellular labeling of CA II protein was identical to that of normal group, but the signal intensity was decreased in cortical collecting duct, markedly increased in the inner stripe of outer medullary and inner medullary collecting ducts, and unchanged in the outer stripe of outer medullary collecting duct. These results suggest that chronic hypokalemia impact the expression pattern of CA II protein depending the portion of the collecting duct.
Animals ; Blotting, Western ; Carbon ; Carbonic Anhydrase II ; Carbonic Anhydrases ; Hypokalemia ; Immunohistochemistry ; Kidney ; Rats

PURPOSE: The histiogenesis of retinoblastoma, the most common intraocular malignancy of childhood, has been investigated from the early times. But in spite of this effort, its origin has been controversial. This study was performed to investigated the cell of origin for retinoblastoma using enzyme histomchemistry for carbonic anhydrase. METHODS: We obtained enucleated eye that was diagnosed as retinoblastoma and its section was stained for hematoxylin-eosin for diagnosis of retinoblastoma. We used enzyme histomchemistry for carbonic anhydrase distinguishing Muller's cells, red-and green-sensistive cones from neuro-retinal cells. RESULTS: They were disagnosed as relatively well-differentiated retinoblastoma by hematoxylin-eosin staining and composed of tumor cells with numerous rosette. Neither numeric nor morphologic changes of Muller cells that are suspected of malignant features in enzyme histochemistry for carbonic anhydrase was found. CONCLUSIONS: The cells of retinoblastoma were originated from the two layers, inner nuclear and ganglion cell layer. The enzyme histochemistry for carbonic anhydrase is the one of the useful methods to investigate the origin of retinoblastoma although more cases is needed to assess.
Carbonic Anhydrase I ; Carbonic Anhydrases ; Diagnosis ; Ependymoglial Cells ; Ganglion Cysts ; Retinoblastoma*

The carbonic anhydrase II (CA-II) is specifically expressed in oligodendrocytes, the cells responsible for myelination in the central nervous system. However no direct evidence on relationship between myelin formation and CA-II immunoreactivity has been described. The aims of these studies are to investigate the relationship between CA-II and myelination during cerebellar development of mouse. Myelin staining was found on postnatal (P) 14, and its intensity increased in proportion to developmental age. CA-II positive oligodendrocytes were observed in the white matter of cerebellum on P 14 day. CA-II positive oligoden-drocytes also occured in the granular layer and Purkinje cell layers in the later stage of dvelopment. The parallel development in the CA-II expression and myelination during development suggests that CA-II in oligoendrocyte play a role to myelination.
Animals ; Carbon* ; Carbonic Anhydrase II* ; Carbonic Anhydrases* ; Central Nervous System ; Cerebellum* ; Mice* ; Myelin Sheath ; Oligodendroglia

Brinzolamide and dorzolamide are highly specific topical carbonic anhydrase inhibitors (CAIs). They lower intraocular pressure (IOP) by reducing the rate of aqueous humour formation without serious side effects. Although systemic CAIs are the most potent medications for lowering intraocular pressure for conditions with ocular hypertension, many cases with adverse systemic reactions have been reported, including Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN). Here, we report 2 cases of TEN that were associated with topical CAIs rather than systemic CAIs.
Carbon ; Carbonic Anhydrase Inhibitors ; Carbonic Anhydrases ; Epidermal Necrolysis, Toxic ; Intraocular Pressure ; Ocular Hypertension ; Stevens-Johnson Syndrome ; Sulfonamides ; Thiazines ; Thiophenes

Methazolamide is a carbonic anhydrase inhibitor commonly used for lowering intraocular pressure in glaucoma and other ophthalmologic diseases. Carbonic anhydrase inhibitors are sulfonamide derivatives that are known to cause many adverse side effects, including dermatologic reactions. Recently, Stevens-Johnson syndrome (SJS) associated with methazolamide treatment has been reported in Japanese and Japanese Americans, and it suggested a relationship between genetic background and methazolamide-induced SJS. We report four cases of SJS induced by methazolamide. Methazolamide should be prescribed with caution in patients of Japanese or Korean descent.
Asian Americans ; Asian Continental Ancestry Group ; Carbonic Anhydrase Inhibitors ; Carbonic Anhydrases ; Glaucoma ; Humans ; Intraocular Pressure ; Methazolamide* ; Stevens-Johnson Syndrome*