Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
This PDF is available to Subscribers Only