Study The Effect Of Sunitinib On The Animal Model Of Retinopathy Of Prematurity

Objective To observe the effectiveness of intravitreal different dosage of Sunitinib for the treatment of retinal neovascularization in animal models, and to explore the relationship between the dosage and the effectiveness.Methods 108 Wistar rats (seven days after birth) were divided into 6 groups(A Air control group, B High oxygen control group, C High oxygen+PBS, D High oxygen+5μg Sunitinib, E High oxygen+ 25μg Sunitinib, F High oxygen+125μg Sunitinib), and 18 rats in each group. Group A was in room air for all the time, the remainder of these groups were exposed to (80±2)% constant oxygen for 5 days and then back to room air for 5 days, other conditions were the same as Group A.When the rats were off the high oxygen, Group C,D,E and F were injected with PBS and corresponding dosage of Sunitinib into the right eyes respectively, leaving the left eyes for own comparison. Group B made no processing. ADPase stained retina was used to evaluate the retinal vascular modality and development. Eyeball pathological section was used to count the pre-retinal endothelial cells. RT-PCR was used to observe the expression of VEGFR-2mRNAResults 1,Retina stretch preparation showed:The retinal vessels sent out from optic disk to periphery with radial pattern and uniform distribution in group A and the peripheral vasculars were normal. The central retinal vessels became constricted and occlusion in high-concentration oxygen environment. While under the relative hypoxia enviroment, the central retinal vessels turned into tortuous and neovascularization was seen in high oxygen group. The number of neovascularization was reduced in varying degrees with the cure of Sunitinib, and the effectiveness of Sunitinib was obvious gradually as the increase in dosage.2,Eyeball pathological section staimed with HE:The average number of neovascular nuclei which breakthrough limiting membrane of amphiblestrodes in the groups A,B,C,D,E,F:2.65±0.875,31.45±0.686,31.60±0.681,26.45±1.099,21.25±1.070,12.55±0.999 respectively. There were significant differences between A and B (P<0.05) and no significant differences between B and C (P>0.05). There were statistical sense among groups C,D,E and F(P<0.05)3,RT-PCR showed:There was a low level of VEGFR-2mRNA in group A. The high-concentration oxygen made the expression of VEGFR-2mRNA cut down, but the relative hypoxia made the expression of VEGFR-2mRNA increased. The expression of VEGFR-2mRNA was reduced in varying degrees with the treatment of Sunitinib, and the effectiveness was obvious gradually along with the increase in dosage. The significant differences were observed at the same time (12d,14d,17d) between A and B (P<0.05). No significant differences were observed between B and C at 17d(P>0.05). There were statistical sense among groups C,D,E and F at 17d (P<0.05).Conlusion 1,Sunitinib can inhibit the generation of neovascularization and the effectiveness of S unitinib was obvious gradually along with the increase in dosage2,The mechanism of inhibition of neovascularization maybe associated with down-regulating the expression of the receptor of vascular endothelial growth factor 2(VEGFR2) mRNA.