J Korean Ophthalmol Soc.  2014 Mar;55(3):416-421. 10.3341/jkos.2014.55.3.416.

The Effects of Topical Carbonic Anhydrase Inhibitors on Nitric Oxide Production in Trabecular Meshwork Cells

• Hong JH
• Kim SE
• Kim JW

• KMID: 2218272
• DOI: http://doi.org/10.3341/jkos.2014.55.3.416

Abstract

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.

Keyword

Brinzolamide; Dorzolamide; Nitric oxide; Topical carbonic anhydrase inhibitor; Trabecular meshwork cells

MeSH Terms

Carbon*
Carbonic Anhydrase Inhibitors*
Carbonic Anhydrases*
Humans
Nitric Oxide*
RNA, Messenger
Trabecular Meshwork*
Carbon
Carbonic Anhydrase Inhibitors
Carbonic Anhydrases
Nitric Oxide
RNA, Messenger

Figure

• 

  Figure 1. Effects of topical carbonic anhydrase ihibitors on the survival of trabecular meshwork cells. Both dorzolamide (D) and brinzolamide (B) did not affect cellular survival at concentrations of 10 and 100 μ M (p > 0.05).

• 

  Figure 2. Effects of topical carbonic anhydrase ihibitors on the production of nitric oxide in trabecular meshwork cells. Dorzolamide (D) increased NO production in a dose-depend-ent manner, which was abolished by co-exposed L-NAME (L) (* p < 0.05).

• 

  Figure 3. Effects of topical carbonic anhydrase ihibitors on the production of nitric oxide in trabecular meshwork cells. Brinzolamide (B) increased NO production in a dose-depend-ent manner which was abolished by co-exposed L-NAME (L) (* p < 0.05).

• 

  Figure 4. Effects of topical carbonic anhydrase inhibitors on the activity of eNOS in trabecular meshwork cells. Exposure to 10, 100 μ M dorzolamide (A) or brinzolamide (B) increased eNOS mRNA expression compared to the non-exposed control.β-actin used as internal standard.

• 

  Figure 5. Effects on the relative expression of eNOS mRNA after exposure to dorzolamide (D) in trabecular meshwork cells. Exposure to 10, 100 μ M dorzolamide increased eNOS mRNA expression compared to the non-exposed control.

• 

  Figure 6. Effects on the relative expression of eNOS mRNA after exposure to brinzolamide (B) in trabecular meshwork cells. Exposure to 100 μ M brinzolamide slightly increased eNOS mRNA expression compared to the non-exposed control.

Reference

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