Abstract
Purpose :
The molecular features of extraocular muscle (EOM) in patients with oculomotor nerve palsy (ONP) remains unrevealed. We tested the hypothesis that lncRNAs and mRNA would been involved in the pathogenesis of ONP.
Methods :
Medial rectus muscle tissues of 16 patients diagnosed with congenital or acquired ONP, and 16 patients diagnosed with constant exotropia (CXT) were collected from the wastes during strabismus surgery.
Patients with any other cranial nerve palsy, any other disease involving the EOMs, previous strabismus surgery or follow-up < 3 months were excluded. Duction deficits of ONP were measured on a -5 to 0 scale.
Four medial rectus muscle tissues from each group were collected for RNA sequencing analysis, followed by functional and pathway enrichment analysis. Co-expression analysis was conducted between differential mRNAs and lncRNAs, followed by target gene prediction of differential lncRNAs. RT-qPCR was applied to validate the expression levels of important lncRNAs and mRNAs, whose clinical significance was examined by receiver operating characteristic (ROC) curve analysis.
Results :
A total of 618 differentially expressed lncRNAs and 322 differentially expressed mRNAs were identified. The up-regulated mRNAs (such as CHI3L1, COL19A1, TECTA, IL1RL1, SPON1 and LRFN2) were significantly related to the components and metabolism of extracellular matrix, while the down-regulated mRNAs were significantly correlated with the composition (such as MYH7, MYL3, MYBPHL, MYH6 and MYOM2) and contraction force (such as MYH7, MYBPHL, MYH6, MYOM2, MYLK2, TNNT1 and TNNI1) of muscle fibres. Co-expression analysis and target gene prediction revealed the strong correlation between down-regulated mRNA MYH7 and down-regulated lncRNA NR_126491.1. Moreover, the differential expressions of lncRNAs (XR_001739409.1, NR_024160.1 and XR_001738373.1) and mRNAs (CDKN1A, MYOG, MYOD1, MYBPH, TMEM64, STATH and MYL3) were validated by RT-qPCR. ROC curve analysis showed that lncRNAs (XR_001739409.1, NR_024160.1 and NR_002766.2) had an AUC > 0.7 and p value < 0.05, as well as mRNAs including CDKN1A, MYOG, MYOD1, MYBPH, TMEM64 and STATH).
Conclusions :
These results may shed light on the molecular biology of EOMs of ONP, as well as the possible correlation of lncRNAs and mRNAs with clinical diagnosis and treatment.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.