Drug-induced apoptosis of trabecular meshwork cells

S. A. Sibayan, M. A. Latina, K. White, Thomas J Flotte

Research output: Contribution to journalArticle

Abstract

Purpose. Apoptosis (programmed cell death) may be triggered by toxic insults. A decrease in the cellularity of the trabecular meshwork (TM) is believed to result from chronic administration of anti-glaucoma medications (timolol, pilocarpine and epinephrine) and dexamethasone. It is our hypothesis that TM cell loss following treatment with these drugs proceeds via the process of apoptosis. The objective of this study is to determine whether in TM cells undergo apoptosis in vitro following incubation with various ophthalmic drugs (timolol, pilocarpine, epinephrine, dexamethasone, and a preservative [benzalkonium chloride]) and anti-metabolites (5-fluorouracil [5-FU] and mitomycin C [MMC]). Methods. Third to fifth passage bovine trabecular meshwork cells were grown to confluence and incubated for 1 to 12 days in growth media with timolol (1-1000 μM), pilocarpine (15-15,000 μM), epinephrine (5-5000 μM), dexamethasone (0.01-100 μM), 0.01% benzalkonium chloride (1:100 to 1:1), 5-FU (10-100 mu;g/ml) and MMC (0.01-100 μg/ml). The cultures were evaluated for apoptosis by phase-contrast microscopy and in situ labeling with the TACS 1 Klenow Apoptosis Screening Kit (Trevigen Inc., Gaithersberg, MD) Results. Timolol (1000 μM), pilocarpine (15,000 μM), epinephrine (500-5000 μM), 0.01% benzalkonium chloride (1:25 to 1:10), MMC (0.1-100 μg/ml) and 5-FU (10-100 μg/ml) induced apoptosis in a dose-dependent manner. TM cells underwent necrosis after 1 day of incubation in 0.01% benzalkonium chloride (1:1). Dexamethasone did not induce apoptosis at any of the concentrations tested. Conclusion. TM cells can undergo apoptosis in response to exposure to timolol, pilocarpine, epinephrine, benzalkonium chloride, 5-FU and MMC. Apoptosis may be a pathway leading to hypocellularity of the TM in eyes that undergo treatment with these medications.

Original languageEnglish (US)
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996
Externally publishedYes

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Trabecular Meshwork
Benzalkonium Compounds
Timolol
Apoptosis
Pilocarpine
Epinephrine
Mitomycin
Pharmaceutical Preparations
Fluorouracil
Dexamethasone
Phase-Contrast Microscopy
Poisons
Glaucoma
Cell Death
Necrosis

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Drug-induced apoptosis of trabecular meshwork cells. / Sibayan, S. A.; Latina, M. A.; White, K.; Flotte, Thomas J.

In: Investigative Ophthalmology and Visual Science, Vol. 37, No. 3, 15.02.1996.

Research output: Contribution to journalArticle

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title = "Drug-induced apoptosis of trabecular meshwork cells",
abstract = "Purpose. Apoptosis (programmed cell death) may be triggered by toxic insults. A decrease in the cellularity of the trabecular meshwork (TM) is believed to result from chronic administration of anti-glaucoma medications (timolol, pilocarpine and epinephrine) and dexamethasone. It is our hypothesis that TM cell loss following treatment with these drugs proceeds via the process of apoptosis. The objective of this study is to determine whether in TM cells undergo apoptosis in vitro following incubation with various ophthalmic drugs (timolol, pilocarpine, epinephrine, dexamethasone, and a preservative [benzalkonium chloride]) and anti-metabolites (5-fluorouracil [5-FU] and mitomycin C [MMC]). Methods. Third to fifth passage bovine trabecular meshwork cells were grown to confluence and incubated for 1 to 12 days in growth media with timolol (1-1000 μM), pilocarpine (15-15,000 μM), epinephrine (5-5000 μM), dexamethasone (0.01-100 μM), 0.01{\%} benzalkonium chloride (1:100 to 1:1), 5-FU (10-100 mu;g/ml) and MMC (0.01-100 μg/ml). The cultures were evaluated for apoptosis by phase-contrast microscopy and in situ labeling with the TACS 1 Klenow Apoptosis Screening Kit (Trevigen Inc., Gaithersberg, MD) Results. Timolol (1000 μM), pilocarpine (15,000 μM), epinephrine (500-5000 μM), 0.01{\%} benzalkonium chloride (1:25 to 1:10), MMC (0.1-100 μg/ml) and 5-FU (10-100 μg/ml) induced apoptosis in a dose-dependent manner. TM cells underwent necrosis after 1 day of incubation in 0.01{\%} benzalkonium chloride (1:1). Dexamethasone did not induce apoptosis at any of the concentrations tested. Conclusion. TM cells can undergo apoptosis in response to exposure to timolol, pilocarpine, epinephrine, benzalkonium chloride, 5-FU and MMC. Apoptosis may be a pathway leading to hypocellularity of the TM in eyes that undergo treatment with these medications.",
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N2 - Purpose. Apoptosis (programmed cell death) may be triggered by toxic insults. A decrease in the cellularity of the trabecular meshwork (TM) is believed to result from chronic administration of anti-glaucoma medications (timolol, pilocarpine and epinephrine) and dexamethasone. It is our hypothesis that TM cell loss following treatment with these drugs proceeds via the process of apoptosis. The objective of this study is to determine whether in TM cells undergo apoptosis in vitro following incubation with various ophthalmic drugs (timolol, pilocarpine, epinephrine, dexamethasone, and a preservative [benzalkonium chloride]) and anti-metabolites (5-fluorouracil [5-FU] and mitomycin C [MMC]). Methods. Third to fifth passage bovine trabecular meshwork cells were grown to confluence and incubated for 1 to 12 days in growth media with timolol (1-1000 μM), pilocarpine (15-15,000 μM), epinephrine (5-5000 μM), dexamethasone (0.01-100 μM), 0.01% benzalkonium chloride (1:100 to 1:1), 5-FU (10-100 mu;g/ml) and MMC (0.01-100 μg/ml). The cultures were evaluated for apoptosis by phase-contrast microscopy and in situ labeling with the TACS 1 Klenow Apoptosis Screening Kit (Trevigen Inc., Gaithersberg, MD) Results. Timolol (1000 μM), pilocarpine (15,000 μM), epinephrine (500-5000 μM), 0.01% benzalkonium chloride (1:25 to 1:10), MMC (0.1-100 μg/ml) and 5-FU (10-100 μg/ml) induced apoptosis in a dose-dependent manner. TM cells underwent necrosis after 1 day of incubation in 0.01% benzalkonium chloride (1:1). Dexamethasone did not induce apoptosis at any of the concentrations tested. Conclusion. TM cells can undergo apoptosis in response to exposure to timolol, pilocarpine, epinephrine, benzalkonium chloride, 5-FU and MMC. Apoptosis may be a pathway leading to hypocellularity of the TM in eyes that undergo treatment with these medications.

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