Molecular profiles in different stages of primary open angle glaucoma – a prospective study

Theme: Glaucoma
What: Glaucoma
Part of: Glaucoma I: Medical / Glaucome I: Médical
When: 5/31/2024, 11:15 AM - 12:45 PM
Where: Room | Salle 801

Abstract

Purpose:

Glaucoma is a sight-threatening condition affecting over 400,000 Canadians and 67 million individuals worldwide. Primary open-angle glaucoma (POAG) constitutes 85-90% of glaucoma cases in developed countries. The prevailing theory suggests that POAG stems from trabecular meshwork (TM) dysfunction, resulting in increased intraocular pressure (IOP). However, some POAG patients continue to deteriorate despite normal IOP, and there has been no study correlating the molecular profile in aqueous humor (AH) with glaucoma progression. This knowledge gap is concerning given glaucoma’s natural history of progression. This project aims to analyze cytokines in AH from POAG patients to establish a correlation with disease severity.

Study Design: Prospective comparative study.

Methods:

Research ethics approvals were obtained from Toronto Western Hospital and Kensington Eye Institute, University of Toronto. Three patient groups (control, mild glaucoma, advanced glaucoma; n = 10 per group) were identified and consented. Glaucoma staging was based on visual field mean deviation values within 6 months of enrollment. AH samples (100 μL per eye) were collected prior to any intraocular surgery. The samples were thawed and subjected to quantitative multiplex cytokine analysis using RayBio® C-Series Human Cytokine Antibody Array C1000.

Results:

Each AH sample underwent analysis of 8000 molecules. Remarkably, when compared to the control and mild glaucoma groups, the advanced glaucoma group exhibited significant changes of proinflammatory cytokines (e.g., interleukin [IL]-1, IL-17, IL-6), immune modulators (CD74, CD40 and CD40 ligand), structural proteins (e.g., matrix metalloproteinases), and mostly intriguingly, angiogenic factors (e.g., angiopoietin-1/2 which played an important role in POAG and primary congenital glaucoma based on animal models and human genetic studies). Gene ontology (GO) analysis highlighted multiple pathways related to immune activation and regulation in the advanced glaucoma group when compared to the mild group.

Conclusions:

This pilot study seeks to correlate disease stages with potential aggravating factors via large-scale molecular analysis. The plethora of identified pathways in advanced POAG patients may collectively contribute to disease progression. Our forthcoming endeavors entail the validation of these pathways within an experimental POAG model, along with a correlation of expression levels with clinical parameters from the same patient cohort. Ultimately, we anticipate that a deeper understanding of the molecular signature of POAG will provide valuable insights for the management and treatment of these patients.

Presenter(s)

Presenting Author: Tianwei Ellen Zhou

Additional Author(s):

David Mathew, Toronto Western Hospital

Karen Wigg, University Health Network

Carmen Balian, Kensington Eye Institute

Irfan Kherani, University Health Network

Matthew Schlenker, University Health Network

Jeremy Sivak, University Health Network

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