Finding Fibrosis

A team of bioinformatics researchers, forged by a collaboration between scientists from several commercial and academic organizations, have recently published in silico findings suggesting that pro-fibrotic signaling pathways may be activated in glaucoma (1). “Like most ophthalmic diseases, glaucoma is age-related. Our team is dedicated to combatting aging and age-related diseases using a computational approach with a broad range of signaling pathway and deep learning tools,” says Alex Zhavoronkov, CEO of Baltimore-based InSilico Medicine, and lead author of the paper (1). “We applied these tools to study glaucoma, and identified pro-fibrotic signatures in the trabecular meshwork and lamina cribrosa which we believe are likely to be causing the disease.” Antonei Csoka, CEO of Vision Genomics and Assistant Professor at Howard University, Washington D.C., comments “We are very excited about these findings – we believe that inflammation and fibrosis are significant factors in the etiology of glaucoma.”

In their research, the team studied microarray gene expression profiles from cultured trabecular meshwork and lamina cribrosa cells, and samples of these tissues from patients with primary open-angle glaucoma (POAG) or healthy controls, obtaining the profiles from publicly available datasets. Using a novel software suite optimized for studying age-related macular degeneration (AMD; 2) and glaucoma, they analyzed the activation of intracellular signaling pathways, and found that elevated levels of TGF-β were associated with the activation of pro-fibrotic pathways (such as AKT) in the trabecular meshwork and lamina cribrosa from patients with POAG. Explaining that their results are “correlations, and future confirmatory studies are warranted to validate these observations” (1), the team propose that the resulting pro-fibrotic processes lead to remodeling of the extracellular matrix, which may impede aqueous humor drainage through the trabecular meshwork and alter the composition of the lamina cribrosa.

Although their findings and hypothesis require validation, the researchers the team are enthusiastic about their next steps, with Zhavoronkov confirming, “We also identified a range of promising anti-fibrotic compounds that are likely to target these signatures, and we will be testing these leads once we secure funding.” Looking further ahead, Csoka comments, “Combined with our previous study on AMD (2), and moving forwards to investigate other ophthalmic diseases including cataract and diabetic retinopathy, we believe we will arrive at a comprehensive understanding of the aging of the human eye which will pave the way towards developing therapies.”