Transplantation of human trabecular meshwork stem cells induces cell proliferation and intraocular pressure reduction in a cell loss model of glaucoma

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.

Author(s): Radhakrishnan Iswarya, Ravinarayanan Haribalaganesh, Srinivasan Senthilkumari, Subbaiah Krishnadas, Chidambaranathan Gowri Priya.

Journal: Graefe's Archive for Clinical and Experimental Ophthalmology

Doi: 10.1007/s00417-026-07202-7

Link: https://www.springermedicine.com/glaucoma/transplantation-of-human-trabecular-meshwork-stem-cells-induces-/52228642

Experimental Paper of the Month manager: Nestor Ventura-Abreu

Editors in Chief: Francesco Oddone, Manuele Michelessi