Growth inhibition of human Tenon's capsule fibroblasts and rabbit dermal fibroblasts with non-carcinogenic N-alkylated anthracyclines.
Bleb fibrosis after glaucoma filtering surgery and proliferative vitreoretinopathy after retinal detachment surgery are complications caused by proliferation of fibroblasts or fibroblastlike cells. The anthracycline daunomycin (DNM) has been used for treatment of those proliferative processes in humans. However, complications such as conjunctival necrosis and corneal or scleral ulcerations have been reported after administration of DNM to glaucoma patients. Intravitreal administration of DNM in rabbit eyes resulted in morphological and functional retinal damage. DNM also has the undesired general effect of carcinogenicity. N-Alkylation of the aminosugar moiety of DNM results in reduction or loss of carcinogenicity. We evaluated the inhibitory effect of the new non-carcinogenic N-alkylated analogues aclacinomycin A (ACA), N,N-dimethyladriamycin (AD280), and N-trifluoroacetyladriamycin-14-O-hemiadipate (AD143) on the growth of cultured human Tenon's capsule fibroblasts and rabbit dermal fibroblasts. Using DNM as a positive control, we conducted proliferation assays that demonstrated that ACA and AD280 inhibited fibroblast growth as effectively as DNM. AD143 was less efficacious. The magnitude of cellular growth inhibition was concentration dependent for all drugs tested. Extension of exposure times resulted in increased rates of cell death. Our in vitro studies suggest that further evaluation of ACA and AD280 should be carried out in animal models of ocular proliferative disorders.
Steinhorst
U H
UH
Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina.
Chen
E P
EP
Freedman
S F
SF
Machemer
R
R
Hatchell
D L
DL
D000818:Animals; D016923:Cell Death; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002675:Child, Preschool; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000166:cytology; D005205:Fascia / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D007223:Infant; D011817:Rabbits; D012867:Skin / Q000166:cytology*
D003630:Daunorubicin