Publications

All publications
June 17, 2016

Pro-fibrotic pathway activation in trabecular meshwork and lamina cribrosa is the main driving force of glaucoma. Cell Cycle.

Written and published by Biogerontology Research Foundation staff in collaboration with Biotime, Inc., Johns Hopkins University, Howard University (Epigenetics Laboratory), Retrope, Inc., Vision Genomics, Inc., and Insilico Medicine, Inc.

Pro-fibrotic pathway activation in trabecular meshwork and lamina cribrosa is the main driving force of glaucoma. Cell Cycle. 2016 Jun 17;15(12):1643-52.

Zhavoronkov A(1,2), Kanherkar RR(3,4), Izumchenko E(5), Teka M(3), Cantor C(6,7), Manaye K(4), Sidransky D(3), West MD(8), Makarev E(1), Csoka AB(3,4).

(1) Insilico Medicine, Inc., ETC, Johns Hopkins University , Baltimore , MD , USA.

(2) The Biogerontology Research Foundation , London , UK.

(3) Vision Genomics, LLC , Washington, DC , USA.

(4)d Epigenetics Laboratory, Howard University , Washington, DC , USA.

(5) Johns Hopkins University, Department of Otolaryngology-Head and Neck Surgery.

(6) Boston University, Boston , MA , USA.

(7) Retrotope, Inc.; Los Altos Hills , CA , USA.

(8) BioTime, Inc., Alameda , CA , USA.

Abstract: While primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide, it still does not have a clear mechanism that can explain all clinical cases of the disease. Elevated IOP is associated with increased accumulation of extracellular matrix (ECM) proteins in the trabecular meshwork (TM) that prevents normal outflow of aqueous humor (AH) and has damaging effects on the fine mesh-like lamina cribrosa (LC) through which the optic nerve fibers pass. Applying a pathway analysis algorithm, we discovered that an elevated level of TGFβ observed in glaucoma-affected tissues could lead to pro-fibrotic pathway activation in TM and in LC. In turn, activated pro-fibrotic pathways lead to ECM remodeling in TM and LC, making TM less efficient in AH drainage and making LC more susceptible to damage from elevated IOP via ECM transformation in LC. We propose pathway targets for potential therapeutic interventions to delay or avoid fibrosis initiation in TM and LC tissues.

Press enquiries
All enquiries should be directed to
info@bg-rf.org.uk