Effect Of Octreotide On Experimental Retinal Neovascularization

Objective: 1. To detect the effect of octreotide on the proliferation of the mouse conjunctival fibroblasts in vitro. 2. To establish a quantifying mice model of oxygen-induced retinopathy, learn the method of counting cell nuclei above the internal limiting membrane in histologic sections, investigate the VEGF expression in retinal. 3. To explore the inhibitory effects of octreotide on the retinal neovascularization and the expression of VEGF, investigate the potential mechanism of its effect.Methods: 1. Primary culture and subculture of conjunctival fibroblasts were established in vitro,using MTT assay observe the effect of octreotide on cells growth. 2. Ten one-week-old mice were exposed to 75% oxygen for 5 days, followed by 5 days room air recovery, the other ten mice of the same age were kept in room air as colltrols.All animals were killed on day 17 of life and both eyes were enucleated, fixed with 4% paraformaldehyde, and embedded in paraffin. The proliferative neovascular response was quanified by counting theendothelial cell nuclei of new vessels above the internal limiting membrane in sections stained with HE. The expression of retina VEGF was detected with immunocytochemistry. 3. Twenty one-week-old mice were divided into two groups randomly. They were all exposed to 75% oxygen for 5 days and then to room air. Each mouse in the treatment group was received intraperitoneal injections of octreotide (50 ug/kg/d) twice for 5 days. The control animals received the same dosage of BSS injection. All animals were killed on day 17 of life and both eyes were enucleated, fixed with 4% paraformaldehyde, and embedded in paraffin,serial axial sections of the retina were obtained,staining with HE or VEGF,investigate the effects of octreotide on the retinal neovascularization and the expression of VEGF. The mice were weighted at the 12th and 17th day respectively,to determine the effect of octreotide on the growth of neonatal mice.Results: 1. The proliferation of the conjunctival fibroblasts was suppressed by octreotide 0.05-50ng/ml. 2. There was a mean of 22 neovascular nuclei per cross-section in hyperoxia compared to less than 1 nuclei per cross-secton in the room air control retinas (P<0.01). Immunohistochemistry of the retinal sections revealed VEGF overexpression in the retinal of the oxygen-treated mice. 3. There was a mean of 22 neovascular nuclei per cross-section in the BSS group compared to 13 nuclei per cross-secton in the octreotide treated retinas (P<0.05). Immuno histochemistry of the retinal sections shown VEGF expression in the retinal was partially inhibited by octreotide injection.There was no significantlyeffect on mice growth by octreotide treatment.Conclusions: Octreotide can inhibit the proliferation of the conjunctival fibroblast in vitro. Retinal angiogenesis can be successfully inhibited by intraperitoneal injections of octreotide, the VEGF expression in the hyperoxia retinal was partial inhibited. The mechanisms of octreotide in inhibit the retinal angiogenesis may contribute to inhibit the activity of some cell and some important growth factors.Octreotide didn't affect the animal growth. These results suggest that octreotide may have potential therapeutic benifits in retinal vascular disease.