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Selection of therapeutic agents for intraocular proliferative disease. Cell culture evaluation
Abstract:
A variety of antimetabolites, steroids, and nonsteroidal anti-inflammatory agents were tested for their ability to inhibit rabbit dermal and conjunctival fibroblast proliferation in cell culture. Doxorubicin hydrochloride and fluorouracil produced notable inhibition in concentrations of less than 1 mg/L. Meclofenamate sodium and indomethacin produced notable inhibition at concentrations of 11 and 40 mg/L, respectively. Dexamethasone sodium phosphate and triamcinolone acetonide produced inhibition at 200 and 150 mg/L, respectively, but paradoxically increased proliferation almost two-fold at concentrations ranging from 1 to 30 mg/L under identical culture conditions. Methotrexate sodium demonstrated only limited effectiveness. This assay system may be a useful approach to drug selection in the treatment of a variety of ocular proliferative disorders. Fluorouracil may prove to be of significant value in the treatment of intraocular proliferative disorders.
Insights
This study evaluated drugs for inhibiting rabbit fibroblast proliferation. Fluorouracil and doxorubicin hydrochloride showed significant inhibition, suggesting potential for treating ocular proliferative disorders.
Area of Science:
- Ophthalmology
- Cell Biology
- Pharmacology
Background:
- Ocular proliferative disorders are a significant cause of vision loss.
- Identifying effective anti-proliferative agents is crucial for treatment.
- Fibroblast proliferation plays a key role in these disorders.
Purpose of the Study:
- To assess the efficacy of various antimetabolites, steroids, and nonsteroidal anti-inflammatory drugs (NSAIDs) in inhibiting rabbit ocular fibroblast proliferation in vitro.
- To identify potential drug candidates for managing ocular proliferative conditions.
Main Methods:
- Rabbit dermal and conjunctival fibroblasts were cultured in vitro.
- Fibroblast proliferation was measured after exposure to different concentrations of various drugs.
- Inhibitory concentrations and paradoxical effects were recorded.
Main Results:
- Doxorubicin hydrochloride and fluorouracil demonstrated significant inhibition at <1 mg/L.
- Meclofenamate sodium and indomethacin showed inhibition at 11 mg/L and 40 mg/L, respectively.
- Corticosteroids (dexamethasone sodium phosphate, triamcinolone acetonide) inhibited proliferation at high concentrations (150-200 mg/L) but paradoxically stimulated it at lower concentrations (1-30 mg/L).
- Methotrexate sodium exhibited limited effectiveness.
Conclusions:
- The in vitro fibroblast proliferation assay is a viable method for screening anti-proliferative drugs for ocular use.
- Fluorouracil shows particular promise for treating intraocular proliferative disorders due to its potent inhibitory effects.
- The biphasic effect of corticosteroids warrants further investigation for ocular applications.