The following is a summary of “Potential Involvements of Anterior Segment Dysgenesis-Associated Genes in Primary Congenital Glaucoma,” published in the December 2024 issue of Ophthalmology by Pyatla et al.
The anterior segment of the eye is essential for maintaining intraocular pressure and vision, with developmental defects leading to anterior segment dysgenesis (ASD) and primary congenital glaucoma (PCG), which share overlapping clinical features, and while several genes have been identified in ASD.
Researchers conducted a retrospective study to explore the potential involvement of ASD-associated genes in the pathogenesis of PCG, considering the significant phenotypic and genotypic overlap.
They performed a nonsystematic search in PubMed using various keyword combinations related to ASD, glaucoma, genetics, and molecular mechanisms, considering articles published until March 2024. Data on ASD-associated genes (FBN1, FOXE3, HMX1, LMX1B, MAF, OTX2, PAX6, PITX2, PITX3, PRDM5, PRSS56, RAX, SLC4A11, SOX2, TRIM44, VAX1, and WT1) were extracted. Gene expressions were analyzed using the GTEx and EMBL-EBI Expression Atlas, and gene interactions were evaluated through the Ingenuity Pathway Analysis software.
The results showed that most ASD-associated genes were highly expressed during early embryonic stages. Interactome analysis revealed that TRIM44, PAX6, WT1, SOX2, OTX2, PRDM5, and FBN1 interacted via the NFκB and Akt/PI3K pathways, either directly or through other partners. FOXC1, PITX2, and HMX1 were involved in Wnt and Hedgehog signaling pathways. Both ASD and PCG shared similar clinical features and mutations in overlapping genes. A hypothetical model was proposed, suggesting 2 parallel mechanisms involving anterior chamber angle defects and cell death in PCG pathogenesis.
Investigators concluded the complex interplay of ASD-associated genes, and the interactions might contribute to the pathogenesis of primary congenital glaucoma by potentially causing defects in the anterior chamber angle and trabecular meshwork and inducing cell death.
Source: tandfonline.com/doi/full/10.1080/08820538.2024.2435944
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