Vascular endothelial cell growth factors promote the in vitro development of rat photoreceptor cells.
We have identified and characterized a novel trophic effect of vascular endothelial cell growth factor (VEGF) on photoreceptor cells. Treatment of retinal cultures, derived from postnatal day 1 (P1) rats, with VEGF-2 resulted in a dose- and time-dependent increase in the level of rhodopsin protein, as determined by ELISA assay. After 7-9 d of treatment the VEGF-1 or VEGF-2, at a concentration of 10 ng/ml, induced a 200-300% increase in rhodopsin protein and a 220% increase in the number of rhodopsin-immunopositive cells. Treatment with VEGF-2 induced a 250% increase in the number of syntaxin-immunopositive cells and a 67% increase in high-affinity GABA uptake, both markers for amacrine cells. In contrast, there was no increase in the non-neuronal cell populations. VEGF-2 induced an approximately 300% increase in the number of bromodeoxyuridine-labeled (BrdU) retinal cells within 48 hr of treatment. After 3 d in culture both the basal and stimulated levels of BrdU incorporation were reduced, suggesting that the proliferative effect of VEGF was restricted developmentally. Furthermore, there was a developmentally dependent increase in the mitogenic response to VEGF-2, with retinal cultures derived from E15, E20, or P1 animals demonstrating a 50, 100, and 300% increase in thymidine incorporation, respectively. However, VEGF treatment resulted in an increase in the number of rhodopsin-immunopositive cells only when the cultures were derived from P1 animals. Therefore, retinal progenitor cells appear to be targets for VEGF, and thus VEGF may be involved in the regulation of the early developmental program of retinal neurogenesis.
Yourey
P A
PA
Departments of Pharmacology and Protein Expression, Human Genome Sciences, Rockville, Maryland 20850, USA.
Gohari
S
S
Su
J L
JL
Alderson
R F
RF
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D010786:Photoreceptor Cells / Q000166:cytology / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D012243:Rhodopsin / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000493:pharmacokinetics
D020934:Ciliary Neurotrophic Factor; D016228:Endothelial Growth Factors; D006133:Growth Substances; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005680:gamma-Aminobutyric Acid; D012243:Rhodopsin