December 2002
Volume 43, Issue 13
ARVO Annual Meeting Abstract  |   December 2002
Mitogen-Activated Protein Kinase (MAPK) Inhibitor PD98059 Inhibits Experimental Choroidal Neovascularization
Author Affiliations & Notes
  • V Woerpel
    Ophthalmology Doheny Eye Institute Keck School of Medicine at the University of Southern California Los Angeles CA
  • F Fujisawa
    Los Angeles CA
  • S He
    Los Angeles CA
  • C Spee
    Los Angeles CA
  • SJ Ryan
    Los Angeles CA
  • DR Hinton
    Los Angeles CA
  • Footnotes
    Commercial Relationships   V. Woerpel, None; F. Fujisawa , None; S. He , None; C. Spee , None; S.J. Ryan , None; D.R. Hinton , None. Grant Identification: Support: NIH grants EY03040, EY01545, the Arnold and Mabel Beckman Foundation and Research to Preven
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 1282. doi:
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      V Woerpel, F Fujisawa, S He, C Spee, SJ Ryan, DR Hinton; Mitogen-Activated Protein Kinase (MAPK) Inhibitor PD98059 Inhibits Experimental Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1282.

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

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Abstract: : Purpose: To determine whether inhibition of the p42/p44 mitogen-activated protein kinase (MAPK) pathway by the MEK inhibitor PD98059 can inhibit the development of laser-induced choroidal neovascularization (CNV) in the rat. Methods: CNV was induced in Long Evans rats by diode laser photocoagulation (75mm, 180mW, 50msec, 4 burns/eye). Three and 6 days after laser application the rats received an intravitreous injection of PD98059 (60mM) or vehicle alone. Fourteen days after photocoagulation, fluorescein angiograms (FA) were taken and graded in a masked fashion. The rats were then sacrificed and the eyes were enucleated, fixed in 4% formalin, and stained with a fluoresceinated endothelial cell specific marker, isolectin B4. Thereafter, sclero-choroidal whole-mounts were created. CNV lesion vascularity was measured by acquiring Z-series confocal images (Zeiss LSM-510), and lesion volume was determined with a Zeiss LSM topography program on reconstructed 3-D images. PD98059 toxicity was assessed by performing electroretinograms (ERG) on dark-adapted rats prior to injection and again 4 and 14 days after injection of drug or vehicle. Results: The FAs showed decreased leakage in the PD98059-treated group (1.8±0.77) compared to controls (2.45±0.35) (p<0.03). Histologic studies showed that the average lesion volume in the PD 98059-treated group (7.2 ±3.5) was reduced by almost 50% compared with the controls (13.8 ±5.0) (p<0.002). Four and 14 days after injection, the ERG showed a normal response amplitude. Conclusion: These data suggest that inhibition of the MAPK signal transduction pathway merits further exploration as an effective means of inhibiting choroidal neovascularization.

Keywords: 346 choroid: neovascularization • 316 animal model • 581 signal transduction: pharmacology/physiology 

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