Etiology of Iridocorneal Endothelial Syndrome: Viral Infection and Immune Suppression.

Purpose: Iridocorneal endothelial (ICE) syndrome is a rare ocular disease affecting the anterior segment, leading to cornea edema and glaucoma. Its unclear etiology limits clinical management to symptomatic interventions. This study uses diverse methodologies to explore potential viral sequences in patients' samples and to elucidate the transcriptomic profiles of ICE cells.

Methods: We used a convenience sampling method, including all eligible patients for analysis. We reviewed polymerase chain reaction (PCR) results for herpes viruses across all samples obtained from ICE syndrome patients at our institution. To further delve into potential pathogenic involvement, we used metagenomic sequencing and whole-genome sequencing techniques on samples. We used smart-seq2 RNA sequencing to explore the transcriptomic features of ICE cells compared with normal cells.

Results: In our PCR tests involving 141 samples, only two positive results were detected in the aqueous humor. Furthermore, the application of metagenomic sequencing on three aqueous humor samples and three corneal endothelium samples, along with whole-genome sequencing on one corneal endothelium sample, yielded no evidence of viral sequences. RNA sequencing revealed upregulated cell growth and neuronal death in ICE cells, alongside downregulated expression in extracellular matrix composition, cell adhesion, and immune response functions.

Conclusions: Our findings from multiple sequencing assays consistently indicate the absence of compelling evidence supporting viral infection in patients with ICE syndrome. Furthermore, the transcriptional analysis of ICE cells reveals a distinct profile characterized by upregulated cell growth and suppressed immune response. Future studies are necessary to validate these findings and improve the generalizability of the results.