Sean Mullany, Tiger Zhou, Ayub Qassim, Henry Marshall, Lachlan S. W. Knight1, Georgina Hollitt, Ella, C. Berry, Thi Nguyen, Shilpa Kuruvilla, Joshua Dubowsky, James Breen, Mark M. Hassall, Sonja Klebe, Stewart Lake, John Landers, Richard A. Mills, Weng O. Chan, Owen M. Siggs, Jamie E. Craig
Purpose: Pseudoexfoliation disease (PEX) is a prevalent yet poorly understood systemic amyloid disease associated with complex polygenic and environmental risk factors. This study seeks to elucidate the pathobiology of PEX through analysis of ribonucleic acid (RNA) sequencing data generated using intraocular surgical specimens collected from disease-affected individuals.
Methods: Whole RNA extracted from anterior lens capsules collected as capsulorhexis samples from routine cataract surgery was subjected to bulk messengerRNA sequencing. Raw transcript read counts of protein coding genes were compared between PEX and non-PEX samples. Differential expression and pathways analyses were performed using established bioinformatic pipelines.
Results: RNA was extracted from samples collected from 28 participants with PEX, and 34 age, gender, and intraocular pressure matched non-PEX controls. All samples successfully underwent library preparation and proceeded to sequencing. Of these, 63 samples passed quality control with a mean mapped read count of 5.2 x 107 per sample. A total of 2882 genes were differentially expressed in PEX lens capsules. Pathways analysis involving differentially expressed genes revealed enrichment of pathways associated with ribosomal function, oxidative stress, protein misfolding, and amyloid disease.
Conclusion: This is the first RNAseq study to investigate the transcriptional architecture of PEX. The results of this study may lead to further insights into the biological processes underlying this common yet enigmatic disease.