Axenfeld-Rieger Syndrome: From Zebrafish Models to Clinical Outcomes

Area of Science:

• Ophthalmology
• Genetics
• Developmental Biology

Background:

• Axenfeld-Rieger Syndrome (ARS) is a genetic disorder affecting eye development.
• Understanding the genetic basis and clinical outcomes is crucial for patient management.

Purpose of the Study:

• To investigate the genetics and clinical outcomes in patients with Axenfeld-Rieger Syndrome.
• To analyze the impact of glaucoma on visual acuity and surgical interventions in ARS patients.
• To utilize a zebrafish model to study the role of FOXC1 variants in ARS.

Main Methods:

• Retrospective cohort study of 66 ARS patients diagnosed between 1970 and 2023.
• Collected data on ocular diagnoses, surgeries, genetic information, and exam findings.
• Employed live-imaging and histological zebrafish studies to investigate FOXC1 variants.

Main Results:

• 42% of patients developed glaucoma, with higher initial IOP and worse final best corrected visual acuity (BCVA).
• Glaucoma patients required more IOP-lowering surgeries, with trabeculectomy and Baerveldt devices showing 10-year survival rates over 70%.
• Zebrafish model with FOXC1 knockdown recapitulated ARS features, confirming the pathogenicity of identified clinical variants.

Conclusions:

• Glaucoma in ARS is associated with poorer visual outcomes and necessitates surgical intervention.
• The study validates FOXC1 variants as a cause of ARS and highlights the utility of zebrafish models for disease research.