FIBRIN GLUE (FG) ENCAPSULATED LIMBAL MESENCHYMAL STEM CELLS (LMSCS) DECREASE BLEB FIBROSIS AREA AFTER TRABECULECTOMY THROUGH TGF- AND MMP-9 MODULATIONEVELYN KOMARATIH, YUYUN RINDIASTUTI, EDDYANTO, HELEN SUSILOWATI, ERYK HENDRIANTO, GATUT SUHENDRO AND FEDIK A. RANTAM
Trabeculectomy is the most common surgical strategy in glaucoma. Postoperative scar remains the leading cause of failure. MSCs hold therapeutic promise for bleb fibrosis, yet the precise mechanisms underlying tissue level changes remain unclear. We hypothesize that fibrin glue encapsulated LMSCs favorably inhibit bleb fibrosis. LMSCs were isolated from rabbit corneoscleral rim by enzymatic digestion method. This was animal study including 4 groups with 10 rabbits in each group. The group including no trabeculectomy and trabeculectomy group, further divided in trabeculectomy only, with subconjunctival FG implantation, and FG encapsulated LMSCs transplantation group. Bleb fibrosis area, expression of TGF-and MMP-9 immunohistochemistry were measured after 21 days. MANOVA and regression analysis were analyzed. Mean fibrosis area of FG (3.67 ± 0.9%) and FG encapsulated LMSCs group (3.69 ± 0.8%) were statistically different compared to trabeculectomy only group (28.6 ± 10.9%; p=0.00). TGF- was significantly decrease in FG encapsulated LMSCs group (1.56 ± 0.5) compared to trabeculectomy only group (2.2 ± 0.5; p=0.019). There was strong correlation between TGF- (=2.03; p=0.002) and MMP-9 (=-1.17 p=0.02) with decreasing fibrosis area in FG encapsulated LMSCs group. FG encapsulated LMSCs had a favorable effect on ECM regulation as well as suppression of TGF-signaling and MMP-9 as negative regulatory of fibrosis in subconjunctival bleb area. Paracrine signaling on modulation of TGF-polarity and MMP-9 activity may contribute to bleb fibrosis inhibition. These data provide insight into the regenerative effects of LMSCs and provide a foundation for clinical application. FG encapsulated LMSCs decrease bleb fibrosis area through TGF- and MMP-9 signaling modulation.
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