[Inhibition of proliferation of retinal pigment epithelium in vitro: vitamin A pharmacodynamics I].
BACKGROUND
In proliferative vitreoretinopathy and choroidal neovascularization, retinal pigment epithelial (RPE) cells proliferate among other cell types. Cell proliferation is controlled by many factors. One such factor is the "superfamily" of nuclear receptors. Ligands of these receptors are vitamin A and D, triiodothyronine and dexamethasone. All-trans-retinal (atR) inhibits human RPE-cell proliferation. AtR binds to the nuclear ligand-dependent transcription factors RAR (retinoic acid receptor) and RXR (retinoid X receptor). Pharmacodynamics of atR were investigated with respect to inhibition of RPE cell proliferation.


METHODS
Primary human RPE cell lines were used up to passage 5. RPE cells were incubated with atR ranging from 1 pM up to 1 microM. AtR was added every other day for 7 days. Cell proliferation was determined by cell counting.


RESULTS
AtR inhibited RPE cell proliferation in a biphasic manner. Two IC50 values were calculated, one in the picomolar range, 10 pM (5-24, 95% confidence interval) and one in the nanomolar range, 17 nM (8-37). Furthermore, inhibition of cell proliferation was examined using specific RAR agonists. Agonists of the RAR-b subgroup inhibited cell proliferation at the lowest concentrations.


CONCLUSIONS
RPE cell proliferation in vitro is inhibited by agonists of RAR. Agonists of the RAR-b subgroup inhibit RPE cell proliferation at the lowest concentrations.
Schönfeld
C L
CL
Universitäts-Augenklinik, München.
D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D020256:Choroidal Neovascularization / Q000473:pathology; D006801:Humans; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects*; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000187:drug effects; D012172:Retinaldehyde / Q000494:pharmacology; D012176:Retinoids / Q000494:pharmacology; D014801:Vitamin A / Q000494:pharmacology*; D018630:Vitreoretinopathy, Proliferative / Q000473:pathology / Q000517:prevention & control*
D018168:Receptors, Retinoic Acid; D012176:Retinoids; D014801:Vitamin A; D012172:Retinaldehyde