Platelet-derived growth factor-BB: a survival factor for the retinal microvasculature during periods of metabolic compromise.
OBJECTIVE
The aim of this study was to test the hypothesis that platelet-derived growth factor (PDGF) reduces ischemia-induced damage to cells in the retinal microvasculature.


METHODS
As a model of ischemia, pericyte-containing microvessels freshly isolated from the adult rat retina were exposed to the inhibitors of ATP synthesis, iodoacetate and antimycin A. Cell viability was assayed by trypan blue exclusion.


RESULTS
PDGF-BB significantly reduced cell death induced by chemical ischemia. The half-maximally effective concentration was approximately 15 pM. In contrast to PDGF-BB, which is the specific ligand for PDGF-beta receptors, ischemic death was not reduced by PDGF-AA, which does not activate the beta-receptors. The protective effect of PDGF-BB was blocked by tolbutamide, which is an inhibitor of ATP-sensitive potassium (K(ATP)) channels and mimicked by the K(ATP) channel opener, pinacidil. Nifedipine, which blocks voltage-gated calcium channels (VGCC's), also mimicked the protective effect of PDGF-BB. Consistent with PDGF-BB and nifedipine preventing cell death via a common mechanism, i.e., reducing VGCC activity, the maximal effects of this growth factor and the calcium channel blocker were not additive.


CONCLUSIONS
Our results indicate that PDGF-BB significantly reduces the vulnerability of retinal microvessels to damage caused by profound ischemia. During episodes of metabolic compromise, it appears likely that the opening of K(ATP) channels via activation of PDGF-beta receptors initiates an adaptive mechanism to enhance the survival of the retinal microvasculature.
Kodama
T
T
Departments of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, Michigan 48105, USA.
Oku
H
H
Kawamura
H
H
Sakagami
K
K
Puro
D G
DG
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D000077214:Becaplermin; D002196:Capillaries; D002470:Cell Survival / Q000187:drug effects; D007461:Iodoacetates / Q000494:pharmacology; D007511:Ischemia / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D012164:Retinal Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D012171:Retinal Vessels / Q000187:drug effects*; D014044:Tolbutamide / Q000494:pharmacology; D014343:Trypan Blue
D007461:Iodoacetates; D010982:Platelet-Derived Growth Factor; D015221:Potassium Channels; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D000968:Antimycin A; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D020797:Receptor, Platelet-Derived Growth Factor beta; D014343:Trypan Blue