Region-Specific Alterations in the Trabecular Meshwork in High- and Low-Tension Glaucoma

This study evaluates histomorphometric and immunohistochemical changes in the ex vivo trabecular meshwork (TM) of high-pressure glaucoma (HPG) and normal tension glaucoma (NTG) compared to controls from donor corneoscleral buttons.

TM specimens were collected from patients with primary open-angle glaucoma (POAG), primary angle-closure glaucoma (PACD), pseudoexfoliation glaucoma (XFG), juvenile open-angle glaucoma (JOAG), and normal-tension glaucoma (NTG) who underwent ab-interno trabeculectomy (2020-2023). Controls were obtained within three to six hours postmortem. The TM beam width in each zone was compared qualitatively with controls and between groups. At the same time, nucleated cell count and epithelial-mesenchymal transformation (EMT) changes were analyzed using ImageJ. Immunohistochemistry was used to identify expression of markers such as angiopoietin-like 1 (ANGPTL1), R-spondin 2 (RSPO2), lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), alpha-smooth muscle actin (α-SMA), and Collagen IV (COLL4) in TM regions across different glaucoma cases and controls.

JOAG, POAG, and PACD exhibited reduced TM beam width, lower nucleated cell counts, and EMT changes in the CSM > JCT regions compared with controls, with JOAG showing the greatest cell loss. XFG and NTG exhibited preserved JCT nucleated cell counts with maximum ANGPTL1 expression in the JCT region in these eyes. Pronounced EMT changes and α-SMA/COLL4 or LYVE1 expression were seen in all glaucoma cases/controls, while RSPO2 expression was seen only in glaucoma.  Conclusions: Distinct histopathological and immunohistochemical changes in TM regions across HTG and NTG suggest different molecular mechanisms of TM damage.