Korean J Ophthalmol.  2011 Aug;25(4):268-274. 10.3341/kjo.2011.25.4.268.

Modulation of Retinal Wound Healing by Systemically Administered Bone Marrow-Derived Mesenchymal Stem Cells

• Chung JK
• Park TK
• Ohn YH
• Park SK
• Hong DS

• KMID: 1018416
• DOI: http://doi.org/10.3341/kjo.2011.25.4.268

Abstract

PURPOSE
To evaluate whether systemically injected bone marrow-derived mesenchymal stem cells (MSCs) can be incorporated into neuroretinal tissues and play an important role in retinal wound healing in the laser-induced retinal trauma model.
METHODS
Retinotomies were made by applying an Nd:YAG laser to rat retina. On the first day after the injuries, cell suspensions that were obtained from the same line of rat (containing 1 x 10(6) green fluorescence protein [GFP]-marked bone marrow-derived MSCs) were injected through a tail vein in the experimental group and phosphate buffer solution (PBS) was injected in the same way in the control group. Fundus photographs were taken serially for fundus examination and eyeballs were enucleated for histological studies that were conducted at five and seven weeks after MSC and PBS injection. After the tissues were prepared, the retinotomy sites were observed with routine histological staining and confocal microscopy.
RESULTS
Retinal detachment resolved in the experimental group, whereas it progressed in the control group. The retinotomy sites closed partially with identifiable GFP positive cells 5 weeks after MSC injection. At 7 weeks after MSC injection, complete healing without retinal detachment and plentiful GFP positive cells were observed at the transitional zone between damaged and normal retina.
CONCLUSIONS
Systemically administered GFP-marked MSCs may be incorporated into the neuroretinal tissues and play an important role in the wound modulation of physically damaged retinal tissues.

Keyword

Mesenchymal stem cells; Retina; Wound healing

MeSH Terms

Animals
*Bone Marrow Transplantation
Disease Models, Animal
Eye Injuries/pathology/*surgery
Mesenchymal Stem Cell Transplantation/*methods
Microscopy, Confocal
Prognosis
Rats
Rats, Sprague-Dawley
Retina/injuries/pathology/*surgery
*Wound Healing

Figure

• 

  Fig. 1 Fundus photographs showing time-dependent fundus changes followed by laser induced retinal trauma in the experimental group (A-C) and control group (D-F). (A) One day after retinotomy, large diffuse subretinal hemorrhages were observed. (B) Three weeks after transplantation, diffuse subretinal hemorrhages subsided compared with previous findings. (C) Definite hemorrhagic lesions were not detected at five weeks after transplantation. (D) One day after retinotomy, thick vitreous hemorrhages with retinal detachments were seen. (E) At three weeks, retinal detachments remained and hemorrhages were observed. (F) At five weeks, retinal detachment (*) remained in the control group.

• 

  Fig. 2 Light microscopy findings for the laser-induced retinotomy site at five and seven weeks after mesenchymal stem cells transplantation in the experimental group. (A) As observed, damaged neurosensory retina lacked continuity (Wright staining, ×100). (B) Note that the lineal cluster of round and dark pigmented cells (arrow) made a retinal hole that was closed partially at the base of the iatrogenic hole area (Wright staining, ×400). (C) Broad healed retinal tissue was seen. A fibrotic horn-like structure (arrow head) seemed to indicate the precise location of laser induced physical trauma. (D) After the wound healing process, the lesion was completely covered with unidentified cells without retinal detachment, however this was different than those of normal neurosensory retina. Only intermingled cell clusters without systemically layered neuronal structures were observed. The outer segment of the photoreceptor cell disappeared abruptly in the transitional zone between healed and undamaged retina.

• 

  Fig. 3 Confocal microscope images of the laser-induced retinotomy site in a continuous section at five and seven weeks after mesenchymal stem cells (MSCs) transplantation (A-C, ×200; D, ×100; E, ×200; F, ×400). (A) Green fluorescence protein (GFP) positive cells were identified in the damaged chorioretinal tissue. (B) Propidium iodide was used for nuclear counterstaining. (C) Merged image of A and B, note that GFP positive cells were perfectly identical to the round, pigmented cells seen in Fig. 2B. (D-F) GFP positive cells originated from MSCs were widely distributed in the healed retina. The number of GFP positive cells increased compared to the images at five weeks after transplantation.

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