Effects of single, short-term exposures of human retinal pigment epithelial cells to thiotepa or 5-fluorouracil: implications for the treatment of proliferative vitreoretinopathy.
OBJECTIVE
To investigate the effects of single, short-term (5 or 30 minutes) exposures to thiotepa or 5-fluorouracil (5-FU) on collagen lattice contraction and retinal pigment epithelial (RPE) cell proliferation.


METHODS
For collagen contraction studies, RPE cells seeded into free floating type I collagen lattices were exposed to single 5 or 30 minute treatments with thiotepa (0.06-4 mg/ml), or 5-FU (0.25-25 mg/ml), or phosphate buffered saline alone as a control. For proliferation studies, RPE cell monolayers were similarly exposed to these agents. The degree of contraction, effects on cell number, and viability were determined up to 14 days after treatment.


RESULTS
Contraction of collagen lattices containing RPE cells and proliferation of RPE cells were significantly inhibited (p < 0.05) by thiotepa and 5-FU at concentrations above 0.06 mg/ml and 0.25 mg/ml respectively (for both 5 and 30 minute treatments), compared with controls. Cell death did not occur except for exposure of the RPE cells in collagen lattices to the highest concentration of thiotepa (4 mg/ml).


CONCLUSIONS
It was concluded that single 5 or 30 minute exposures to thiotepa or 5-FU significantly inhibited collagen contraction and the proliferation of RPE cells. These findings suggest that short, single, non-toxic exposures to thiotepa or 5-FU which can be reproduced clinically may be useful in the modulation of proliferative vitreoretinopathy.
Department of Pathology, Institute of Ophthalmology, London.
C H
CH
Kon
N L
NL
Occleston
A
A
Foss
C
C
Sheridan
G W
GW
Aylward
P T
PT
Khaw
D000477:Alkylating Agents / Q000494:pharmacology*; D000963:Antimetabolites / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects*; D013852:Thiotepa / Q000494:pharmacology*; D018630:Vitreoretinopathy, Proliferative / Q000188:drug therapy
D000477:Alkylating Agents; D000963:Antimetabolites; D003094:Collagen; D013852:Thiotepa; D005472:Fluorouracil