Liu Dan, Xia Xiao-Bo, Xu Xue-Liang, Tian Xiao-Feng, Shang Lei
Department of Ophthalmology, Xiangya Hospital of the Central South University, Changsha 410013, Hunan Province, China.
Int J Ophthalmol. 2011;4(2):137-42. doi: 10.3980/j.issn.2222-3959.2011.02.05. Epub 2011 Apr 18.
To explore the role of unc5b in retinal neovascularization in murine oxygen-induced retinopathy (OIR).
On postnatal 7(P7), C57BL/6J mice were exposed to 75%±2% oxygen for 5 days. On postnatal 12(P12), the mice were brought back to the room air (21% oxygen) to induce retinal neovascularization. Western blot analysis was performed to examine the temporal expression of unc5b in murine retinas. Double staining for unc5b and isolectin B4 were employed to determine the location of unc5b in murine retinas. The effect of unc5b on retinal neovascularization was evaluated by intravitreal injection of unc5b-FC in mice with OIR. Retinal neovascularization was measured by counting neovascular cell nuclei above the internal limiting membrane and by angiography of flat-mounted retinas perfused with fluorescein dextran.
Compared to age-matched normal mice, the expression of unc5b was significantly increased in retinas of OIR mice on P17 and P21. Unc5b was apparently expressed in retinal vessels of OIR while being negative in normal retinal vessels. Retinal neovascularization in eyes injected with unc5b-FC was significantly reduced.
Unc5b-FC can effectively inhibit retinal neovascularization induced by OIR. It may serve as a powerful and novel therapy for ischemia-induced retinal disease.
探讨unc5b在小鼠氧诱导性视网膜病变(OIR)视网膜新生血管形成中的作用。
出生后第7天(P7),将C57BL/6J小鼠置于75%±2%氧气环境中5天。出生后第12天(P12),将小鼠放回正常空气中(21%氧气)以诱导视网膜新生血管形成。采用蛋白质免疫印迹分析检测unc5b在小鼠视网膜中的表达时间。采用unc5b与荆豆凝集素B4双重染色确定unc5b在小鼠视网膜中的定位。通过向患有OIR的小鼠玻璃体内注射unc5b-Fc来评估unc5b对视网膜新生血管形成的影响。通过计数内界膜上方新生血管细胞核以及对灌注荧光素葡聚糖的平铺视网膜进行血管造影来测量视网膜新生血管形成。
与年龄匹配的正常小鼠相比,OIR小鼠视网膜中unc5b的表达在P17和P21时显著增加。Unc5b在OIR的视网膜血管中明显表达,而在正常视网膜血管中为阴性。注射unc5b-Fc的眼睛视网膜新生血管形成显著减少。
Unc5b-Fc可有效抑制OIR诱导的视网膜新生血管形成。它可能成为治疗缺血性视网膜疾病的一种强大而新颖的疗法。