Transplantation of human trabecular meshwork stem cells induces cell proliferation and intraocular pressure reduction in a cell loss model of glaucoma.
Iswarya Radhakrishnan, Haribalaganesh Ravinarayanan, Senthilkumari Srinivasan, Krishnadas Subbaiah, Priya Chidambaranathan Gowri
AI Summary
This study found transplanted trabecular meshwork stem cells reduced intraocular pressure and increased cell proliferation in a glaucoma model, suggesting a potential therapy for outflow pathway dysfunction.
Abstract
Purpose
This study aimed to evaluate the therapeutic potential of trabecular meshwork stem cells (TMSC) transplantation in enhancing the trabecular meshwork (TM) cell proliferation and intraocular pressure (IOP) reduction in a cell loss human organ cultured anterior segment (HOCAS) model of glaucoma.
Methods
A cell loss HOCAS model of glaucoma was established using saponin. IOP was monitored at regular intervals, and immunohistochemistry was performed to quantify the cell loss. Qtracker-labeled cultured TMSCs (3 × 10⁵ cells/500µl) were transplanted into the model, with periodic monitoring of IOP changes. After five days of transplantation, tissues were subjected to immunohistochemistry (ABCG2, p75) to evaluate the localization of the transplanted stem cells. The effectiveness of the transplanted cells in promoting TM proliferation was further evaluated by Ki67 staining.
Results
The saponin treatment in the HOCAS model resulted in 32.08 ± 4.74% cell death and decrease in the outflow facility by 15% at day 6. Transplantation of cultured TMSCs into this model mitigated the outflow resistance induced by saponin and increase the outflow by 38%. Confocal microscopic analysis confirmed the homing of transplanted TMSCs to both filtering and non-filtering regions of the TM. Additionally, TMSC transplantation resulted in a significant increase in TM cell proliferation, which was 17.94 ± 4.45% compared to the sham treatment, which showed 5.29 ± 4.2%.
Conclusions
The cell loss HOCAS model for glaucoma was established using saponin which resulted in IOP increase and TM cell loss. Further, in this model, the transplanted TMSCs, home to TM, and resulted in the reduction of IOP which was increased upon saponin treatment. The TMSC transplantation also enhanced TM cell proliferation.
Shields Classification
Key Concepts4
A cell loss human organ cultured anterior segment (HOCAS) model of glaucoma was established using saponin, resulting in 32.08 ± 4.74% cell death and a 15% decrease in outflow facility at day 6.
Transplantation of cultured human trabecular meshwork stem cells (TMSCs) into a saponin-induced cell loss HOCAS model mitigated the outflow resistance and increased outflow by 38%.
Transplantation of cultured human trabecular meshwork stem cells (TMSCs) into a saponin-induced cell loss HOCAS model resulted in a significant increase in trabecular meshwork (TM) cell proliferation (17.94 ± 4.45%) compared to sham treatment (5.29 ± 4.2%).
Confocal microscopic analysis confirmed the homing of transplanted Qtracker-labeled human trabecular meshwork stem cells (TMSCs) to both filtering and non-filtering regions of the trabecular meshwork in a saponin-induced cell loss HOCAS model.
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