1120-6721/051-09$04.50/0 C.P. JUÁREZ 1 , J.C. MUIÑO 1 , H. GUGLIELMONE 2 , R. SAMBUELLI 3 , J.R. ECHENIQUE 1 , M. HERNÁNDEZ 1 , J.D. LUNA 1 European Journal of Ophthalmology / Vol. 10 no. 1, 2000 / pp. 51-59 Experimental retinopathy of prematurity: angiostatic inhibition by nimodipine, ginkgo-biloba, and dipyridamole, and response to different growth factors PURPOSE. To investigate whether commonly used vasodilating drugs ameliorate angiogen- esis in experimental retinopathy of prematurity (ROP), and to study the response of these drugs to different growth factors. METHODS. We used a rat and mouse model of oxygen-induced ischemic retinopathy. Ani- mals were treated with nimodipine, gingko-biloba and dipyridamole intraperitoneally start- ing the day before exposure to room air (day 1). Controls were injected with vehicle solu- tion only. Eyes were processed histopathologically with serial sections and neovascular- ization was measured by counting the nuclei within the retinal internal limiting membrane, by a masked observer. Retinal and vitreous tissues were assayed by ELISA for VEGF, PDGF and TGFβ2. RESULTS. Nimodipine significantly inhibited the growth of new vessels in rats. The number of nuclei was 310 ± 69 in the control group (n:14) and 121 ± 53 in the treated ones (n:14), (p<0.0005). Similar results were found with ginkgo-biloba extracts: 344 ± 53 (n:15) in con- trols, and 136 ± 29 (n:11) in treated ones (p<0.0005), and with dipyridamole: 303 ± 69 (n:13) in controls, and 131 ± 48.5 in treated rats (p<0.0005). Results were similar in mice. 186 ± 45 (n:7) nuclei counted in controls against 90 ± 25 (n:6) for dipyridamole treated (p<0.0005); and 81 ± 21 for ginkgo-biloba treated animals (p<0.0005). A gradual, very significant increase in VEGF values in response to relative hypoxia (room air) contrasted with the significant inhibition noted both with ginkgo-biloba extracts and dipyridamole. TGFβ2 and PDGF both showed a gradual increase in relative hypoxia at days 2 and 4 of room air (p<0.0005). Treated animals showed marked inhibition of the three growth factors. CONCLUSIONS. All three drugs markedly inhibited angiogenesis in experimental ROP. Growth factors were elevated in hypoxic conditions. Treated animals showed significant decreas- es of PDGF, VEGF, and TGFβ2 in retinal and vitreous tissues. (Eur J Ophthalmol 2000; 10: 51-9) KEY WORDS: Neovascularization, Angiogenesis, Nimodipine, Ginkgo-biloba, Dipyridamole Accepted: August 30, 1999 © by Wichtig Editore, 2000 1 Fundación VER, Córdoba 2 L.A.C.E. Laboratories, Córdoba 3 Catholic University of Córdoba, Córdoba - Argentina Juarez 8-03-2000 13:14 Pagina 51