Abstract
Purpose :
Ischemic retinopathies (IRs) are major ocular disorders leading to visual impairment. These pathologies are characterized by an initial phase of microvascular degeneration that lead to a second phase of retinal pathological neovascularization (NV). microRNAs (miRNAs) are a family of non-coding RNAs acting as negative regulators of gene expression and playing a key role in blood vessel development and pathological NV. However, the post-transcriptional modulation of miRNAs in the eye during the development of IRs is still poorly understood. This study aims to identify the alterations on miRNAs expression-profiling in both retina and choroid during the two pathological phases of IRs.
Methods :
Next generation sequencing (NSG) technology was used to perform a complete miRNAs expression profiling in both retinal and choroidal tissues from OIR rat and healthy (CTRL) animals. We identified potential miRNAs target genes mediating angiogenesis in OIR by using in sillico approach assessed according the algorithms of miRSystem database.
Results :
NSG analyses showed that ~20% of the total miRNAs expressed were significantly altered in their expression (up- or down-regulation) and 6% of the total were found highly expressed in the retina and choroid from rats subjected to OIR. During OIR-induced vessel degeneration, we found 31 miRNAs altered in their expression in the retina and 45 in the choroid. Moreover, during pathological NV, we found 3 miRNAs (miR-30a, -30e, -190b-) strongly downregulated ( >70% of reduction), and 2 miRNAs (miR-30d, -335) highly upregulated (>400% of increase) in the retina of OIR animals. While in the choroid, let-7f-and miR-126a were the most reduced miRNAs (>85% ) and miR-125a, let-7e, let-7g the most increased miRNAs (>600%). Furthermore, bioinformatical analyses of predicted angiogenic targets showed miR-1b, -30a, -126a, -96 as new potential targeted genes with pro-angiogenic functions and miR-199a, -125b with anti-angiogenic functions. Finally, we identify a serial of OIR-modulated miRNAs predicted to target angiogenic key factors including VEGF, VEGFR2, IFG-1, HIF-1a and EPO.
Conclusions :
This is the first study showing retinal/choroidal miRNAs profiling in OIR by NSG technology. Our results provide a strong framework for the characterization and possible therapeutic approach of specific miRNAs that contributing in regulating ocular angiogenesis in IRs.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.