Abstract
Purpose :
Pentosan polysulfate sodium (PPS) is a sulfated polysaccharide used to relieve bladder pain and discomfort related to interstitial cystitis. Recently, long-term exposure to PPS was linked to the pathogenesis of an insidious maculopathy, but the specific mechanism remains elusive. Here we investigated the effects of PPS on retinal pigment epithelium (RPE) gene transcription to identify potential biochemical pathways that could be involved in PPS maculopathy.
Methods :
RPE cell line (ARPE-19) was cultured until confluency, and then treated with a high dose of PPS (1mg/ml) for 72h. RNA from treated cells and controls in triplicates were sequenced on Illumina platforms. The resulting data was gathered for bioinformatic analysis. Functional enrichment analysis was performed using the Gene Ontology (GO), KEGG, Reactome, Disease Ontology (DOSE) and DisGeNET pathway databases. Significance was established when adjusted p values (padj) <0.05.
Results :
486 genes were differentially expressed out of 10897 co-expressed genes between groups. Functional analysis showed a significant enrichment of extracellular matrix organization (padj=7.53e-12), blood vessel morphogenesis (padj=7.53e-12), response to wounding (padj=4.18e-7), regulation of signaling receptor activity (padj=6.33e-9) and growth factor binding (padj=4.65e-7) pathways. Significantly enriched disease-associated pathways included retinal disease (padj=1.47e-6), inflammation (padj=1.46e-6), retinal vascular disease(padj=6.51e-5), retinal degeneration(padj=6.51e-5), disease of capillaries (padj=2.6e-4) and age-related macular degeneration (padj=9.7e-4).
Conclusions :
PPS treatment modified the transcriptomic profile of RPE cells, significantly altering pathways associated with extracellular matrix maintenance, vascular development, and growth factor binding and signaling. Disturbance of these pathways could contribute to the outer retinal injury observed clinically. These data provide new insights on the pathogenic mechanisms of PPS maculopathy.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.