miRNA involvement in angiogenesis in age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Late-stage AMD is characterized by choroidal neovascularization (CNV). miR-93 appears to play a role in regulating vascular endothelial growth factor-A (VEGF-A), a known factor involved in neovascularization. Understanding its biological significance might enable development of therapeutic interventions for diseases like AMD. We aimed to determine the role of miR-93 in AMD using a laser-induced CNV mouse model. CNV was induced by laser photocoagulation in C57BL/6 mice. The CNV mice were transfected with scrambled miR or miR-93 mimic. The treatment effect was assessed by fundus photography and fluorescein angiography and confirmed by choroidal flatmount. The expression of miR-93 and VEGF-A in ocular tissues was analysed by quantitative polymerase chain reaction (qPCR) and Western blot. The overexpression effects of miR-93 were also proved on human microvascular endothelial cells (HMECs). Significantly decreased expression of miR-93 was observed by qPCR analysis in CNV mice compared to untreated mice (p < 0.05). VEGF-A messenger RNA (mRNA) and protein expression were upregulated with CNV; these changes were ameliorated by restoration of miR-93 (p < 0.05). CNV was reduced after miR-93 transfection. Transfection of miR-93 reduced the proliferation of HMECs (p < 0.01), but no significant changes were observed in 2D capillary-like tube formation (p > 0.05) and migration (p > 0.05) compared with that in the untreated cells. miR-93 has been shown to be a negative modulator of angiogenesis in the eye. All together, these results highlight the therapeutic potential of miR-93 and suggest that it may contribute as a putative therapeutic target for AMD in humans.

miR‐539‐5p inhibits experimental choroidal neovascularization by targeting CXCR7

“…Accumulating evidence indicates that aberrantly expressed miRNAs play important roles in AMD progression (17,19). Given that CXCR7 is an important regulator of angiogenesis, in the current study, we focused on miRNAs that target to CXCR7.…”

“…Recent studies in animals and humans have revealed important functions of miRNAs in the development and progression of wet AMD (15)(16)(17). Thus far, several miRNAs with proangiogenic (miR- 23, -27, and -155) or antiangiogenic (miR-31, -150, -24, -29, and -93) functions have been identified by using the laser-induced CNV murine model, a wellestablished model that closely mimics the pathogenesis of AMD in humans (18)(19)(20)(21)(22)(23)(24); however, it remains unclear whether other miRNAs, especially those that target to CXCR7, are also involved in the process of angiogenesis in CNV.…”

The Inhibitory Effects of Gold Nanoparticles on VEGF-A-Induced Cell Migration in Choroid-Retina Endothelial Cells

“…It is physiologically required for regulating proliferation and assembling endothelial cells during vasculogenesis, as well as for their maintenance and survival throughout the lifetime of blood vessels [23]. However, under subtle pathological alterations, abnormal angiogenesis with retinal and choroidal microvascular alterations have been observed during PDR, high myopia, and neovascular AMD [24][25][26].…”

New strategies in achieving antiangiogenic effect: Multiplex inhibitors suppressing compensatory activations of RTKs

“…27 Proangiogenic factors have also been verified as targets for treatment of obesity 28 and diabetic retinopathy. 29,30 AMD is characterized by pathological angiogenesis 31 and its treatment has been revolutionized by antiangiogenic agents. 32 In summary, pathological angiogenesis is involved in cancers and various non-neoplastic diseases.…”