Abstract
Purpose :
Idiopathic epiretinal membrane (ERM) is a disease of the macula in which a fibrocellular tissue causes contraction and distortion of the retinal surface, which can lead to distorted or reduced vision. Surgery is the only current treatment, but operating too early can be unnecessary, whilst operating too late leaves residual distortion and blur. We used RNA-seq to investigate the transcriptome and therefore the active cellular processes leading to the pathogenesis of ERM in human surgical samples, comparing to control vitrectomy for idiopathic physiological, uncomplicated PVD (uPVD)
Methods :
Membranes peeled from 14 patients with ERM and vitrectomy samples from 5 patients having uPVD had RNA extracted and converted to cDNA using the SMARTseq v4 Ultra Low Input RNA kit. NEBNext Ultra II DNA Library Prep Kit for Illumina was used to create libraries for sequencing, which were run on an Illumina MiSeq. HISAT2 was used to build an index and HTSeq to provide count tables. DESeq was used for differential gene expression analysis. Reactome path analysis was used for gene ontology.
Results :
RNA was obtained in 13 patients with ERM and 3 patients with uPVD. cDNA was obtained in 11 patients with ERM and 1 patient with uPVD. Counts ranged from 263797 to 696637. Alignment rate varied from 29 to 68%. Significant differential gene expression was observed by heatmap and volcano plot between ERM and uPVD samples. The top three over-represented pathways using Reactome were 'extracellular matrix organisation', 'integrin cell surface interactions' and 'assembly of collagen fibrils and other multimeric structures'. Manual inspection of these upregulated pathways in ERM identified integrins α-1, α-3, α-11 and β-4, which are a novel finding in this study.
Conclusions :
The identification of upregulation of integrins α-1, α-3, α-11 and β-4 in epiretinal membranes is a new and exciting finding. Integrins have a critical role in linking the cell and extracellular matrix and play a role in cell migration and transition from quiescent to proliferative states. Anti-integrin therapies, including risuteganib, THR-687 and SF-0166 are being investigated for use in retinovascular diseases including diabetic macular oedema and age-related macular degeneration, but this study suggests that epiretinal membrane is another possible indication for these therapies.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.