May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
The MAP Kinase Pathway and VEGF are Involved in IGF-1-Stimulated Proliferation of Human Retinal Pigment Epithelial Cells (hRPE)
Author Affiliations & Notes
  • C. Y. Weng
    Dept. of Ophthalmology & Visual Sciences, Kellogg Eye Center-University of Michigan, Ann Arbor, Michigan
  • P. C. Kothary
    Dept. of Ophthalmology & Visual Sciences, Kellogg Eye Center-University of Michigan, Ann Arbor, Michigan
  • M. A. Del Monte
    Dept. of Ophthalmology & Visual Sciences, Kellogg Eye Center-University of Michigan, Ann Arbor, Michigan
  • Footnotes
    Commercial Relationships  C.Y. Weng, None; P.C. Kothary, None; M.A. Del Monte, None.
  • Footnotes
    Support  The Skillman Foundation
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 861. doi:https://doi.org/
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    • Get Citation

      C. Y. Weng, P. C. Kothary, M. A. Del Monte; The MAP Kinase Pathway and VEGF are Involved in IGF-1-Stimulated Proliferation of Human Retinal Pigment Epithelial Cells (hRPE). Invest. Ophthalmol. Vis. Sci. 2008;49(13):861. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose:
 

Abnormal proliferation and metaplasia of human retinal pigment epithelial cells (hRPE) have been implicated in the development of proliferative vitreoretinopathy. The purpose of this study is to investigate the stimulation by insulin-like growth factor-1 (IGF-1) on the proliferation of hRPE and elucidate the role of MAP kinase in the IGF-1 signaling cascade.

 
Methods:
 

Human RPE cells were harvested from postmortem non-pathological eyes. Cellular proliferation in the presence of increasing concentrations of IGF-1 and IGF-1 + PD98059 (an inhibitor of MAP kinase) was measured by 3H-thymidine incorporation and trypan blue exclusion (T) studies. Under the same experimental conditions, synthesis of vascular endothelial growth factor (VEGF) was measured utilizing 14C-methionine immunoprecipitation and immunocytochemical methods. Data were analyzed using Microsoft Excel.

 
Results:
 

IGF-1 stimulates hRPE cellular proliferation in a dose-dependent manner as demonstrated using 3H-thymidine incorporation and T. The maximal effect of IGF-1 was observed at a concentration of 50 ng/ml. There was also a concentration-dependent IGF-1-induced increase in VEGF synthesis demonstrated by 14C-methionine-VEGF immunoprecipitation. This was qualitatively confirmed by immunocytochemical staining using anti-VEGF and rhodamine-conjugated anti-rabbit IgG. Again, the maximal effect of IGF-1 was seen at 50 ng/mL. PD98059 suppressed both IGF-1-induced cell proliferation (694.58 ± 81.48 vs. 6208.50 ± 1252.62, CPM ± SEM, n = 8, p < 0.001) as well as IGF-1-stimulated VEGF production (967.98 ± 151.22 vs. 2997.58 ± 588.87, CPM ± SEM, n = 8, p < 0.05). Cells remained viable and healthy after exposure to PD98059 as determined by T.

 
Conclusions:
 

These studies suggest that IGF-1 is a mitogen for hRPE cells, possibly by stimulating synthesis of the angiogenic factor VEGF. Additionally, PD98059 inhibits IGF-1-induced production of VEGF and hRPE proliferation, suggesting that the MAP kinase pathway is involved in IGF-1-mediated angiogenesis.  

 
Keywords: retinal pigment epithelium • growth factors/growth factor receptors • proliferative vitreoretinopathy 
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