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Yiqin Du, HONGMIN YUN, Yi Zhou, Enzhi Yang; Trabecular Meshwork Regeneration by Stem Cells. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4675. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To explore the hypothesis that human trabecular meshwork stem cells (TMSCs) have the ability to home to laser-damaged TM region in mice and regenerate the damaged TM tissue and reduce intraocular pressure (IOP).
C57BL/6 mouse TM tissue was partially damaged by laser photocoagulation using a 532nm green laser. After laser damage, 50,000 of either human TMSCs or fibroblasts were injected intracamerally. Cells were prelabeled with a membrane dye Vybrant DiO before injection. Untreated, laser treated or medium injected mice following laser were served as controls. IOP was measured regularly up to 4 weeks after laser and cell injection. The location of injected cells was detected by confocal microscopy on wholemounts and cryosections. Expression of TM cell markers CHI3L1, MGP; fibrotic markers SPARC, fibronectin; inflammatory markers CD45, CD11b, F4/80 was examined by immunofluorescent staining or by quantitative real-time PCR on the mouse TM tissue. TM structure was compared by transmission electron microscopy (TEM).
At two weeks and four weeks after intracameral injection, TMSCs localized specifically to the laser damaged TM region and reduced mouse IOP. In contrast, injected fibroblasts were distributed nonspecifically and increased IOP. Human CHI3L1 and MGP were detected in the TM tissue of mice with human TMSC injection but not in controlled mice. Laser treatment dramatically increased the expression of SPARC, FN, CD45, CD11b and F4/80 on mouse TM. With TMSC injection, the expression of SPARC, FN, CD45, CD11b and F4/80 was suppressed at both 2 weeks and 4 weeks. TM structure damaged by laser was regenerated in TMSC injected eyes but not the eyes with fibroblast injection at 2 weeks and 4 weeks.
Human TMSCs have the ability to home to laser-damaged TM region, reconstruct the TM structure and reduce IOP in mice. This suggests a potential of stem cell-based therapy for reconstruct the conventional outflow pathway and prevention of glaucomatous vision loss.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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