Cyclic 3',5'-adenosine monophosphate modulates retinal pigment epithelial cell migration in vitro
S. Hackett, Z. Friedman and P. A. Campochiaro
Retinal pigment epithelial (RPE) cell migration has been implicated in the
pathogenesis of proliferative vitreoretinopathy (PVR). Using a modified
Boyden chamber assay, we have examined the effect of cyclic nucleotides on
human RPE cell migration in vitro. Dibutyryl cyclic 3',5'-adenosine
monophosphate (cAMP) (10(-3) mmol/L) inhibits RPE cell random migration by
83%, fibronectin-induced chemotaxis by 61%, and platelet-derived growth
factor-induced chemotaxis by 68%. Random and directed migration of RPE
cells is not significantly affected by 8-bromo cyclic 3',5'-guanosine
monophosphate. Agents that significantly increase intracellular levels of
cAMP are also inhibitors of RPE cell migration. Though there is a fairly
good correlation for most drugs for their ability to stimulate cAMP
production and their ability to inhibit cell migration, it is not perfect,
suggesting that some drugs may modulate migration by more than one
mechanism. Timolol blocked both the isoproterenol-induced stimulation of
RPE adenylate cyclase and attenuated the ability of isoproterenol to
inhibit RPE migration. These data suggest that cAMP may modulate RPE cell
migration in an inhibitory fashion. Elucidation of the biochemical events
involved in RPE cell migration could provide information that might be
useful in planning a strategy to attempt pharmacologic control of
proliferative vitreoretinopathy.
