Glaucoma Can Develop Following Hepatitis C-Associated Inflammation

Inflammation following a hepatitis C virus (HCV) infection appears to set off a chain reaction of inflammatory responses, including one associated with altered expression of glaucoma biomarker genes, according to results of a study published in Clinical Ophthalmology. “Expression of these genes in response to an inflammatory stimulus also provides additional evidence that inflammation should be considered a possible risk factor for glaucoma through a variety of pathways,” the researchers explain. 

Investigators at the University of Missouri-Kansas City searched publication databases for potential gene biomarkers for glaucoma. They extracted fold-change data from a previously published study for differentially expressed responsive genes in macrophages and peripheral blood mononuclear cells from individuals with chronic HCV and those who had cleared the virus. They then evaluated the patient records for changes in glaucoma biomarker expression.

No glaucoma-causing genes have been identified; however, inflammation and oxidative stress are known contributors. The investigators found evidence linking 372 unique genes with glaucoma and narrowed the list down to the top 50 genes.

When the list of candidate genes was filtered for polyinosinic:polycytidylic acid [poly(I:C)] responsiveness, in samples from individuals with cleared HCV, 17 of the candidate genes were found to be differentially expressed. Three of the 17 genes had log₂ fold-changes of at least 1.5, or -1.5 or less (glutathione peroxidase I [GPX1], growth arrest-specific protein 7 [GAS7], matrix metalloproteinase-9 [MMP9]).

In addition, in samples from individuals with cleared infection stimulated with a toll-like receptor 3 (TLR3) agonist, seven genes involved in the antioxidant response had decreased expression and expression of 6 genes involved in immune response had increased expression.

Comparing the samples from individuals with chronic and cleared HCV revealed that 6 genes had differing expression patterns. One of the genes (GPX1) was found to have log₂ fold-changes of at least 1.5, or -1.5 or less. Together, these data indicated that clearing HCV led to a partial reversal in endothelin-1 (EDN1), catalase (CAT), and neural cell adhesion molecule 1 (NCAM1) expression change and increased the expression of GPX1 and phospholipid-transporting ATPase ABCA1 (ABCA1).

This study was limited by not having access to ophthalmological data from individuals who provided blood samples.

“This study provides a first step towards determining whether there is a genetic component in secondary glaucoma due to viral infection, opening the door for future studies in both human and animal models as to whether a genetic component exists in the development of secondary glaucoma and whether there exist actionable targets for medical intervention,” the researchers explain.

Reference

Player JK, Riordan SM, Duncan RS, Koulen P. Analysis of glaucoma associated genes in response to inflammation, an examination of a public data set derived from peripheral blood from patients with hepatitis C.Clin Ophthalmol. 2022;16:2093-2103. doi:10.2147/OPTH.S364739