The Research Of Treatment Of TNP470 On Retinopathy Of Prematurity

Object: Retinopathy of prematurity is a disease which badly affect the life of premature babies. It is commonly caused by premature, low birth weight, oxygen therapy after birth. The pathogenesis of ROP is not very clear still, but recent research indicate that retinal neovascularization may play the dominant effect. The retinal blood vessel starts to grow in embryo sixteenth week. Until the embryo thirty-second week, the developing retinal blood vessel extend to the nasal side .when the embryo become mature the retinal blood vessel extend to the temporal side. The retinal vessel of prematurity is not developed which is the basic pathophysiological characteristics of ROP. when the prematurity exposed to higher-than-in normal oxygen concentration , the developing capillary buds are dropout. When the baby is taken to the normal oxygen concentration . This pathologic vessel exaggerates the normal angiogenic process, and large retinal neovascularizations produce. These vessels are pathologic vessels which lose normal density and shape and lead to proliferation retinopathy even retinal detachment. Vascular endothelial growth factor(VEGF)and other angiogenic factors are upregulated. As more and more studies focus on inhibiting neovascularization, we establish an animal model of Oxygen-Induced Retinopathy of prematurity to explore the inhibitory effect of TNP470 on retinal neovascularization.Methods:sixty 7-day-old C57BL/6J mice were devided into five groups that include large-dosage group ,small-dosage group, high and normal oxygen control groups. Forty-eight mice were putted into the environment with 75% oxygen for 5 days to establish models of vascular proliferation retinopathy. The two experimental groups were given TNP470 by subcutaneous injection at the dose of 30mg·kg-1 and 10mg·kg-1 respectively twice a day for five days while the control groups was given the same volume of alcohol (3%) subcutaneously.The ADPase histochemical technique was applicated for retinal flat mount to assess the oxygen-induced change of tetinal blood vessels. The inhibitory effect of TNP470 on retinal neovascularization was evaluated by counting the endotheliocyte nuclei of new vessels which extended from retina to vitreous in the tissue-slice of HE staining. Immunocytochemistry was performed on some of cross-sections of the retina by using an endothelial cell-specific antibody CD34.Results: There were large retinal neovascularization in the high concentration oxygen group compared with in the normal air condition group, and the density and shape of retinal neovascularization were disordered. This result indicated that the animal model of Oxygen-Induced Retinopathy of prematurity was successful. Comparing with high concentration oxygen group, regular distributions and reduced density of retinal neovascularization were observed in the TNP 470 treatment group. The number of the endotheliocyte nuclei of new vessels extending from retina to vitreous was less in the TNP470 treatment group than in high concentration oxygen group (P<0.001). The difference of the number of new blood vessels endotheliocyte nuclei in two treatment groups was not significant (P>0.05). Immunocytochemistry staining showed CD34 positive cells localized in the vitreal side of the inner limiting membrane in the retinal sections of oxygen-treated eyes.Conclusion: Retinal neovascularization can be inhibitted by subcutaneous injection of TNP470. worthy of further investigate.