Li-Li Tian1, Bing Ren2, Xiao-Wei Gao2, Ying Luo2, Yan Cai2, Kun Zhou1, An-Jie Du3, Yong Zhao2. 1. Medical College of Shihezi University, Shihezi 832000, Xinjiang Uygur Autonomous Region, China ; Ophthalmic Center, No.474 Hospital of Chinese PLA, Urumqi 830013, Xinjiang Uygur Autonomous Region, China. 2. Ophthalmic Center, No.474 Hospital of Chinese PLA, Urumqi 830013, Xinjiang Uygur Autonomous Region, China. 3. Department of Ophthalmology, Yuncheng Central Hospital, Yuncheng 044000, Shanxi Province, China.
Abstract
AIM: To investigate the effect of intravitreal injection administered sorafenib, a multikinase inhibitor, in a rat model of oxygen-induced retinopathy (OIR). METHODS: Seven-day-old Sprague-Dawley rats (n=144) were randomly assigned to six groups. Group A received normal partial oxygen pressure and groups B, C, D, E and F were exposed to hyperoxia (75±2)% from postnatal 7d (P7) to P12 to induce retinopathy of prematurity. The rats in groups C, D, E and F were received intravitreal injections of either vehicle (DMSO) or sorafenib at P12 (5, 20 and 80 µg, respectively). Then they returned to normoxia after P12. The retinas were whole-mounted and imaged with a confocal microscopy. The vascular branching points were counted to quantify neovascularization at P17. Cross-sections of the retina were stained with hematoxylin and eosin (HE). The nuclei of new vessels breaking the internal limiting membrane were counted to quantify the proliferative neovascular response. RESULTS: The retinal vessel in groups B and C turned into tortuosity and a great deal of neovascularization were observed. Sorafenib-treated rats had significantly less neovascularization as compared with vehicle-treated and control rats in a dose dependent manner (P<0.05). The number of vascular branching points in A, B, C, D, E and F were 16.50±3.90, 37.44±6.47, 37.08±5.10, 30.80±6.85, 26.08±5.08 and 19.83±3.51, respectively. The number of the nuclei of retinal new vessel in A, B, C, D, E and F were 0.22±0.42, 35.66±4.70, 35.30±4.54, 27.30±4.28, 21.41±3.53, and 7.41±2.87, respectively. There were significant difference between each group (P<0.05) except groups B and C. CONCLUSION: In the rat OIR model, sorafenib could inhibit retinal neovascularization in a dose dependent manner.
AIM: To investigate the effect of intravitreal injection administered sorafenib, a multikinase inhibitor, in a rat model of oxygen-induced retinopathy (OIR). METHODS: Seven-day-old Sprague-Dawley rats (n=144) were randomly assigned to six groups. Group A received normal partial oxygen pressure and groups B, C, D, E and F were exposed to hyperoxia (75±2)% from postnatal 7d (P7) to P12 to induce retinopathy of prematurity. The rats in groups C, D, E and F were received intravitreal injections of either vehicle (DMSO) or sorafenib at P12 (5, 20 and 80 µg, respectively). Then they returned to normoxia after P12. The retinas were whole-mounted and imaged with a confocal microscopy. The vascular branching points were counted to quantify neovascularization at P17. Cross-sections of the retina were stained with hematoxylin and eosin (HE). The nuclei of new vessels breaking the internal limiting membrane were counted to quantify the proliferative neovascular response. RESULTS: The retinal vessel in groups B and C turned into tortuosity and a great deal of neovascularization were observed. Sorafenib-treated rats had significantly less neovascularization as compared with vehicle-treated and control rats in a dose dependent manner (P<0.05). The number of vascular branching points in A, B, C, D, E and F were 16.50±3.90, 37.44±6.47, 37.08±5.10, 30.80±6.85, 26.08±5.08 and 19.83±3.51, respectively. The number of the nuclei of retinal new vessel in A, B, C, D, E and F were 0.22±0.42, 35.66±4.70, 35.30±4.54, 27.30±4.28, 21.41±3.53, and 7.41±2.87, respectively. There were significant difference between each group (P<0.05) except groups B and C. CONCLUSION: In the rat OIR model, sorafenib could inhibit retinal neovascularization in a dose dependent manner.
Entities:
Keywords:
neovascularization; retinopathy of prematurity; sorafenib; tyrosine kinase inhibitors
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