March 28, 2023

Inflammation implicated in exfoliation syndrome

Computational genetics tools have implicated inflammatory pathways in exfoliation syndrome, the most common cause of secondary glaucoma, which can result in blindness.

Exfoliation syndrome (XFS) — an age-related systemic disorder that causes excessive production and accumulation of abnormal extracellular material — is the most common cause of secondary glaucoma, which can result in blindness. More than 60 genetic variants are associated with XFS, but the exact pathophysiological processes of XFS are unclear. 

To identify roles for specific genes and clarify the biology underlying XFS, Jibril Hirbo, PhD, and colleagues performed transcriptome-wide association studies (TWAS) combined with a computational genetics tool called PrediXcan that correlates genetically regulated gene expression with traits. 

The TWAS genes they identified for XFS were enriched for genes associated with inflammatory conditions. They found that mRNA levels for six genes were significantly decreased in iris tissues from XFS patients compared to control samples. 

The results, reported in BMC Genomics, implicate inflammatory pathways in XFS and suggest that targeting these pathways may be a therapeutic option to reduce progression in XFS.

Other VUMC authors include Eric Gamazon, PhD, Patrick Evans, PhD, Priyanka Pawar, Julia Sealock, PhD, Ran Tao, PhD, Peter Straub, Anuar Konkashbaev, Max Breyer, Karen Joos, MD, PhD, and Nancy Cox, PhD. They were joined by collaborators at Friedrich‑Alexander‑Universität, Erlangen, Germany, University of Cambridge, Cambridge, UK, and Genome Institute of Singapore. 

The research was supported by the National Institutes of Health (grants EY021453, HG010718, EY008126) and Research to Prevent Blindness.