Transcriptomics Analysis of Lens from Patients with Posterior Subcapsular Congenital Cataract

Area of Science:

• Ophthalmology and Genetics
• Molecular Biology

Background:

• Posterior subcapsular congenital cataract (PSCC) is a significant cause of childhood visual impairment.
• Understanding the molecular mechanisms underlying PSCC is crucial for developing effective interventions.

Purpose of the Study:

• To investigate the transcriptional landscape of PSCC using mRNA sequencing.
• To identify differentially expressed genes (DEGs) and candidate genes involved in PSCC aetiology.

Main Methods:

• mRNA sequencing was performed on lens epithelial cells and lens cortex/nuclear fibers from PSCC patients and normal children.
• Differential gene expression analysis was conducted using stringent statistical criteria (p-value < 0.05, FDR < 0.05).
• Bioinformatic databases (iSyTE, Cat-Map) were used to filter and prioritize candidate genes.

Main Results:

• 1533 DEGs were identified in lens epithelial cells, with 847 downregulated and 686 upregulated.
• Stricter criteria revealed 551 DEGs (97 upregulated, 454 downregulated) in epithelial cells.
• 1263 DEGs were found in lens cortex and nuclear fibers, with 646 downregulated and 617 upregulated.
• Downregulated genes in epithelial cells were enriched in pathways related to lens structure, development, and fiber cell differentiation.
• Candidate genes GRIFIN, HTRA1, and DAPL1 were identified as potentially significant in PSCC.

Conclusions:

• Transcriptional dysregulation plays a key role in the pathogenesis of posterior subcapsular congenital cataract.
• Specific downregulated genes in lens epithelial cells are associated with critical lens functions.
• Identified candidate genes may serve as novel targets for PSCC diagnosis and treatment.