Abstract
Purpose :
Purpose: Glaucoma remains a leading cause of irreversible visual impairment and blindness worldwide. Moreover, there is a higher prevalence of glaucoma in individuals of African and Latinx descent compared to European descent individuals. A primary risk factor for glaucoma is elevated intraocular pressure (IOP), resulting in biomechanical aberrations of the eye, including the optic nerve head (ONH). The ONH cells, ONH astrocytes and lamina cribrosa (LC) cells respond to biomechanical signals. Previously, our research group has demonstrated that glaucoma LC cells derived from European descent donors have dysregulated expression of profibrotic and anti-fibrotic microRNAs (miRNAs). In this study, we investigated if miRNAs were altered in the LC cells of normal African descent donors when compared to normal European donors.
Methods :
Primary human normal LC cells of European descent donors (n=3 strains) and African descent donors (n=2 strains) were derived from human ONH explants. LC cells from each strain were grown to 100% confluency. PCR arrays were used to determine if expression changes were altered for miRNAs associated with fibrosis. The expression fold changes were normalized to SNORD95 and SNORD96A using the Qiagen analysis software. Subsequently, the bioinformatics tool TargetScan was utilized to predict mRNA targets for miRNA differences between the two populations.
Results :
miRNA PCR arrays showed altered expression of multiple miRNAs in LC cells. The fold regulation of miRNA-29a (-1.90) and -29c (-2.64) were decreased in African descent donors. Predictive mRNA targets for miR-29 include extracellular matrix genes such as various types of collagens.
Conclusions :
miRNA differences were observed in African descent donors when compared to European donors. For example, miRNA-29a and -29c expression levels were decreased in LC cells derived from African descent donors. miRNA-29 targets fibrotic genes to stimulate a profibrotic environment causing remodeling of the ONH. Thus, the alteration of miRNA-29 may contribute to the prevalence of glaucoma in individuals of African descent.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.