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Effects of dopamine antagonists and agonist on cultured human Tenon's fibroblast cells
1Department of Ophthalmology, Kaohsiung Medical College, Taiwan, Republic of China.
Abstract:
It was found that long-term therapy with topical antiglaucoma drugs may increase the number of fibroblasts and inflammatory cells in the conjunctiva and Tenon's capsule then decrease the success of glaucoma filtering surgery. Since some dopamine antagonists and agonists are reported to have ocular hypotensive effects, they could potentially be used as clinical antiglaucoma agents in future. In this study, several dopamine antagonists and agonists were evaluated in their effects on the fibroblast proliferation of ocular tissues with cultured human ocular Tenon's fibroblast cells. It was found that dopamine antagonists inhibited [3H]-thymidine uptake to 10.8%, 14.4%, 42.2% and 72.4% of control in domperidone, 28.6%, 67.7%, 96.9% and 99.2% in haloperidol, 9.8%, 18.9%, 103.5% and 104.6% in moperone and 9.8%, 24.7%, 70.8% and 96.9% in loxapine respectively, while the 0.5% concentration of drugs were dissolved in dimethyl sulfoxide (DMSO) followed by dilution in culture medium to final concentrations ranging from 0.05%, 0.005%, 0.0005% to 0.00005%. In the case of dopamine agonist, bromocriptine, the proliferation of cultured human Tenon's fibroblast cells was also inhibited for 25.1% of the control at 0.05% concentration and 92.3% of the control at 0.00005% concentration. These results indicate that these dopamine drugs have a potential long-term application in the treatment of glaucoma without having the stimulating effect on the proliferation of human Tenon's fibroblast cells.
Insights
Certain dopamine drugs may offer a new glaucoma treatment. They inhibit fibroblast proliferation, potentially improving glaucoma surgery success rates without stimulating ocular tissue growth.
Area of Science:
- Ophthalmology
- Pharmacology
- Cell Biology
Background:
- Long-term topical antiglaucoma drugs can negatively impact glaucoma surgery outcomes by increasing conjunctival fibroblasts and inflammatory cells.
- Dopamine antagonists and agonists show potential for ocular hypotensive effects, suggesting a future therapeutic role in glaucoma management.
Purpose of the Study:
- To evaluate the effects of various dopamine antagonists and agonists on the proliferation of human ocular Tenon's fibroblast cells.
- To determine if these compounds could be developed into glaucoma treatments that do not stimulate fibroblast proliferation.
Main Methods:
- Human ocular Tenon's fibroblast cells were cultured.
- Dopamine antagonists (domperidone, haloperidol, moperone, loxapine) and a dopamine agonist (bromocriptine) were applied at varying concentrations (0.05% down to 0.00005%).
- Inhibition of fibroblast proliferation was measured by [3H]-thymidine uptake.
Main Results:
- Dopamine antagonists significantly inhibited fibroblast proliferation in a dose-dependent manner.
- Bromocriptine also demonstrated significant inhibition of fibroblast proliferation.
- The tested dopamine drugs showed potential for long-term glaucoma treatment without adverse effects on fibroblast proliferation.
Conclusions:
- Dopamine antagonists and agonists effectively inhibit human Tenon's fibroblast proliferation in vitro.
- These findings suggest that dopamine-modulating drugs could be a promising new class of agents for glaucoma treatment.
- Further research into these compounds may lead to improved glaucoma therapies with better surgical outcomes.