ObjectiveTo investigate whether intravitreally applied haemangioblasts (HB) derived from human embryonic stem cells (hESCs) are helpful for the repair of vascular damage caused in animals by an oxygen-induced retinopathy (OIR), by an induced diabetic retinopathy (DR) or by an induced retinal ischaemia with subsequent reperfusion. MethodsHuman embryonic stem cell-derived HBs were transplanted intravitreally into C57BL/6J mice (OIR model), into male Wistar rats with an induced DR and into male Wistar rats undergoing induced retinal ischaemia with subsequent reperfusion. Control groups of animals received an intravitreal injection of endothelial cells (ECs) or phosphate-buffered saline (PBS). We examined the vasculature integrity in the mice with OIR, the blood-retina barrier in the rats with induced DR, and retinal thickness and retinal ganglion cell density in retina flat mounts of the rats with the retinal ischaemic-reperfusion retinopathy. ResultsIn the OIR model, the study group versus control groups showed a significantly (p<0.001) smaller retinal avascular area [5.12.7%;n=18 animals versus 12.2 +/- 2.8% (PBS group; n=10 animals) and versus 11.8 +/- 3.7% (EC group; n=8 animals)] and less retinal neovascularization [6.3 +/- 2.5%;n=18 versus 15.2 +/- 6.3% (n=10; PBS group) and versus 15.8 +/- 3.3% (n=8; EC group)]. On retinal flat mounts, hESC-HBs were integrated into damaged retinal vessels and stained positive for PECAM (CD31) as EC marker. In the DR model, the study group versus the EC control group showed a significantly (p=0.001) better blood-retina barrier function as measured at 2days after the intravitreal injections [study group: 20.2 +/- 12.8l/(gxhr); n=6; versus EC control group: 52.9 +/- 9.9l/(gxhr; n=6)]. In the retinal ischaemia-reperfusion model, the groups did not differ significantly in retinal thickness and retinal ganglion cell density at 2, 5 and 7days after baseline. ConclusionBy integrating into damaged retinal vessels and differentiating into ECs, intravitreally administered hESC-HBs may have partially repaired a retinal vascular injury caused by OIR model and DR.
基金：
Beijing New Star of Science and Technology Program [H020821380190, Z131102000413025]; Fund of the Work Committee for Women and Children of the China State Department [2014108]; National Natural Science Fund Projects of China [30471861]; Biocompatibles UK Ltd. [20120263794]; University of Heidelberg (Heidelberg, Germany) [3 070 101]
第一作者机构：[1]Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Inst Ophthalmol,Beijing Key Lab Ophthalmo, Beijing, Peoples R China
通讯作者：
通讯机构：[1]Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Inst Ophthalmol,Beijing Key Lab Ophthalmo, Beijing, Peoples R China[*1]Beijing Institute of Ophthalmology 17 Hougou Lane, Chong Wen Men 100005 Beijing China
推荐引用方式(GB/T 7714)：
Wang Jin-Da,An Ying,Zhang Jing-Shang,et al.Retinal vascular injuries and intravitreal human embryonic stem cell-derived haemangioblasts[J].ACTA OPHTHALMOLOGICA.2017,95(6):E468-E476.doi:10.1111/aos.13477.
APA：
Wang, Jin-Da,An, Ying,Zhang, Jing-Shang,Wan, Xiu-Hua,Zhang, Wei...&Xu, Liang.(2017).Retinal vascular injuries and intravitreal human embryonic stem cell-derived haemangioblasts.ACTA OPHTHALMOLOGICA,95,(6)
MLA：
Wang, Jin-Da,et al."Retinal vascular injuries and intravitreal human embryonic stem cell-derived haemangioblasts".ACTA OPHTHALMOLOGICA 95..6(2017):E468-E476
