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Yiqin Du, Yi Zhou, Enzhi Yang, HONGMIN YUN; Trabecular Meshwork Stem Cells Have Higher Affinity to TM cells. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3278.
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© ARVO (1962-2015); The Authors (2016-present)
Previously we described that stem cells from the trabecular meshwork (TMSCs) home to the TM region after intracameral injection in normal mice. In current study, we explore whether human TMSCs can home to laser-damaged TM region in mice and whether TMSCs have higher affinity to TGF-beta 2 treated TM cells.<br />
Mouse TM was damaged for 180° arc by laser photocoagulation. After laser, 50,000 of either human TMSCs or fibroblasts were injected intracamerally. Normal and laser treatment only mice were served as controls. Intraocular pressure (IOP) was measured regularly for 2 weeks after laser and cell injection. The location of DiO prelabeled cells was detected by confocal microscopy on tissue wholemounts and cryosections. Expression of human specific antibody CHI3L1, fibrotic marker SPARC and inflammatory marker CD45 was examined by immunofluorescent staining. Cell viability was evaluated by TUNEL staining. Chemotaxis and affinity of TMSCs was performed with TM cells with or without TGF-beta 2 treatment. Gene expression changes were detected by qPCR.<br />
At two weeks after intracameral injection, TMSCs localized specifically to the 180° arc damaged TM region and reduced the IOP. In contrast, injected fibroblasts were detected in the whole TM region, cornea and iris and increased IOP. Increased expression of SPARC and CD45 was detected in laser treated and fibroblast injected eyes. Injected cells were viable at 2 weeks after injection. TM cells treated with TGF-beta 2 were more effective for attraction of TMSC migration and attachment. TMSCs had the most affinitive to the TM cells than TM cells and fibroblasts. After TGF-beta 2 treatment, the expression of collagen5A1 and SPARC in TM cells increased significantly which may be contributed to increased affinity to TMSCs.<br />
Human TMSCs have the ability to home to laser-damaged TM region. Glaucomatous factor TGF-beta 2 treated TM cells are more attractive for TMSC migration and affinity. This suggests the potential of stem cell-based therapy for TM homeostasis restoration and reduction of IOP.<br />
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