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miRNA involvement in angiogenesis in age-related macular degeneration

Journal of Physiology and Biochemistry volume 72, pages 583–592 (2016)Cite this article

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.

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Acknowledgment

We would like to thank the staff of EMSU for their assistance with animal care.

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Affiliations

  1. Eye Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, China

    Lei Wang, Ping Liu & Hong Zhang

  2. Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, VIC, Australia

    Amy Yi Wei Lee

  3. Drug Delivery Unit, Centre for Eye Research Australia, Melbourne, VIC, Australia

    Amy Yi Wei Lee

  4. Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, 32 Gisborne Street, East Melbourne, VIC, 3002, Australia

    Jonathan P. Wigg, Hitesh Peshavariya & Hong Zhang

Authors
  1. Lei Wang
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  2. Amy Yi Wei Lee
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  3. Jonathan P. Wigg
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  4. Hitesh Peshavariya
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  5. Ping Liu
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  6. Hong Zhang
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Correspondence to Ping Liu or Hong Zhang.

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Wang, L., Lee, A.Y.W., Wigg, J.P. et al. miRNA involvement in angiogenesis in age-related macular degeneration. J Physiol Biochem 72, 583–592 (2016). https://doi.org/10.1007/s13105-016-0496-2

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  • DOI: https://doi.org/10.1007/s13105-016-0496-2

Keywords

  • miR-93
  • Age-related macular degeneration
  • Choroidal neovascularization
  • VEGF-A
  • HMEC