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Editors Selection IGR 15-4

Basic Science: A new potential pathogenic pathway

Comment by Tina Wong on:

69029 Pro-fibrotic pathway activation in trabecular meshwork and lamina cribrosa is the main driving force of glaucoma, Zhavoronkov A; Kanherkar RR; Izumchenko E et al., Cell cycle (Georgetown, Tex.), 2016; 15: 1643-1652

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Zhavoronkov et al. provides an insightful perspective of the role of signaling pathways governing extracellular matrix regulation on the development and progression of glaucoma. By using bioinformatics to evaluate human trabecular meshwork and lamina cribosa tissue samples, the authors provide a signaling pathway activation profile for glaucoma specifically affecting the extracellular matrix composition in the lamina cribosa and trabecular meshwork outflow facility. The authors report that certain signaling pathways such as p38 act to protect the trabecular meshwork from increases in IOP and ILK activity affects extracellular matrix remodeling following mechanical stretching of the trabecular meshwork from elevated IOP. With regards to the lamina cribrosa, there are signaling pathways identified that can provide a protective effect to withstand increases in IOP, which may provide an explanation to why certain eyes do not develop glaucoma despite an increase in IOP. The authors conclude that the connection between fibrosis and glaucoma progression, in relation to trabecular meshwork and lamina cribrosa structural integrity, will enable future research to discover and develop new therapeutics that target the scleral tissue surrounding key structures that play a major role in the development of glaucoma as a novel approach for the management of disease progression.

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