Human bone marrow mesenchymal stem cells for retinal vascular injury.
OBJECTIVE
To examine the potential of intravitreally implanted human bone marrow-derived mesenchymal stem cells (BMSCs) to affect vascular repair and the blood-retina barrier in mice and rats with oxygen-induced retinopathy, diabetic retinopathy or retinal ischaemia-reperfusion damage.


METHODS
Three study groups (oxygen-induced retinopathy group: 18 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received BMSCs injected intravitreally. Control groups (oxygen-induced retinopathy group: 12 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received an intravitreal injection of phosphate-buffered saline. We applied immunohistological techniques to measure retinal vascularization, spectroscopic measurements of intraretinally extravasated fluorescein-conjugated dextran to quantify the blood-retina barrier breakdown, and histomorphometry to assess retinal thickness and retinal ganglion cell count.


RESULTS
In the oxygen-induced retinopathy model, the study group with intravitreally injected BMSCs as compared with the control group showed a significantly (p = 0.001) smaller area of retinal neovascularization. In the diabetic retinopathy model, study group and control group did not differ significantly in the amount of intraretinally extravasated dextran. In the retinal ischaemia-reperfusion model, on the 7th day after retina injury, the retina was significantly thicker in the study group than in the control group (p = 0.02), with no significant difference in the retinal ganglion cell count (p = 0.36).


CONCLUSIONS
Intravitreally implanted human BMSCs were associated with a reduced retinal neovascularization in the oxygen-induced retinopathy model and with a potentially cell preserving effect in the retinal ischaemia-reperfusion model. Intravitreal BMSCs may be of potential interest for the therapy of retinal vascular disorders.
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital of Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, China.
Jin-Da
JD
Wang
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital of Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, China.
Ying
Y
An
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital of Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, China.
Jing-Shang
JS
Zhang
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital of Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, China.
Xiu-Hua
XH
Wan
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital of Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, China.|Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Seegartenklinik, Heidelberg, Germany.
Jost B
http://orcid.org/0000-0003-2972-5227
JB
Jonas
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital of Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, China.
Liang
L
Xu
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital of Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, China.
Wei
W
Zhang
D000818:Animals; D000831:Animals, Newborn; D016026:Bone Marrow Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D013508:Ophthalmologic Surgical Procedures; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000175:diagnosis / Q000601:surgery; D012164:Retinal Diseases / Q000175:diagnosis / Q000209:etiology / Q000601:surgery*
blood-retina barrier; bone marrow mesenchymal cells; diabetic retinopathy; neuroprotection; neuroregeneration; retinal protection; retinal regeneration; retinal vascular injury; retinopathy of prematurity