Transcriptomic Study of Mechanism Driving Conjunctival Fibrosis Following Glaucoma Filtration Surgery.

Background

Glaucoma filtration surgery (GFS) is performed to slow down disease progression in glaucoma, a leading cause of irreversible blindness worldwide. Following surgery, pathological wound healing may lead to conjunctival fibrosis and filtering failure. Myofibroblast transition of human Tenon's fibroblast (HTF) is responsible for postoperative conjunctival scarring, with TGFβ signalling playing a key role in this process. However, the detailed molecular mechanism underlying myofibroblast transition in HTF remain understudied.

Methods

In this study, we performed transcriptomic analysis to delineate the TGFβ1-induced changes in the transcriptome of HTF. HTF was isolated from three patients following GFS and treated with TGFβ1 for 5 days, followed by RNA-seq for transcriptomic profiling.

Results

Our results identified 3362 differentially expressed genes (DEGs) in HTF following TGFβ1 treatment, of which 1532 were upregulated and 1820 were downregulated. Using gene ontology analysis, we identified signalling pathways associated with the pathogenesis of conjunctival fibrosis, including pathways involved in myofibroblast differentiation, TGFβ-signalling, collagen and extracellular matrix organisation, epithelial to mesenchymal transition, and cell cycle regulation. This study provided detailed characterisation of the transition from HTF to myofibroblast, and highlighted key genes that are upregulated (LDLRAD4, CDKN2B, FZD8, MYOZ1) and downregulated (SOD3, LTBP4 and RCAN2) in this myofibroblast transition process.

Conclusions

Overall, this study provided insights into the transcriptional landscape of HTFs and myofibroblast differentiation, which has important implication to understanding the pathophysiology of conjunctival scarring and development of new therapeutic agents.