Intracamerally transplanted stem cells changed the segmental outflow pattern and reduced intraocular pressure in a mouse glaucoma model

Abstract

Purpose : Primary open-angle glaucoma is associated with pathological changes of the trabecular meshwork (TM). TM stem cells (TMSCs) preferentially home to the injured TM tissue for regeneration (Yun et al. Communi Biol. 2018; 1: 216). The hypothesis of this study was that intracamerally transplanted TMSCs can change the segmental outflow pattern for IOP regulation in a glaucoma mouse model.

Methods : Human TMSCs were labeled with Vybrant dye DiO and 5 x 10⁴ cells were intracamerally transplanted into a primary open-angle glaucoma model of mice with transgenic myocilin (Myoc) Y437H mutation (Tg-MyocY437H, a kind gift from Dr. Gulab Zode, UNTHSC) as well as wildtype mice as controls. Human corneal fibroblasts were injected as a control. Mouse IOP was measured before cell injection and at 3 weeks after injection. At 3 weeks, anterior segment optical coherence tomography (OCT) was performed to evaluate central corneal thickness (CCT) and the anterior chamber angle. Then microbead perfusion was performed and mice were sacrificed. Wholemount staining on the TM was evaluated on a confocal microscope for quantifying the high-flow, low-flow, and no-flow region. Statistical analysis was done by one-way ANOVA followed by the Tukey posttest to assess the significance.

Results : TMSC injected mice showed similar CCT and anterior angle to the control groups (both p>0.05), which indicates there was no effect on the CCT and the angle of TMSC injection, and the IOP measurement was not affected by CCT. With TMSC transplantation, Tg-MyocY437H mice had reduced IOP, increased high-flow length, and lowered no-flow length than controls (no injection, sham injection, and fibroblast inject) (all p<0.05). The same change was observed in wildtype mice and there was no statistical difference between Tg-MyocY437H and wildtype mice. TMSCs distributed to the TM high-flow, low-flow, and no-flow regions.

Conclusions : TMSC intracameral transplantation can upregulate aqueous humor outflow and reduce IOP which is partially by increasing the high-flow region and reducing the no-flow region in mice

This is a 2021 ARVO Annual Meeting abstract.