June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Inhibition of miR-21 prevents abnormal angiogenesis and subretinal fibrosis in an experimental model of choroidal neovascularization
Author Affiliations & Notes
  • Albert Xiong
    Ophthalmology, Augusta University, Augusta, Georgia, United States
  • Menaka Thounaojam
    Ophthalmology, Augusta University, Augusta, Georgia, United States
  • Qiuhua Yang
    Vascular Biology Center, Augusta University, Augusta, Georgia, United States
  • Ravirajsinh Jadeja
    Biochemistry and Molecular Biology, Augusta University, Augusta, Georgia, United States
  • Pamela M Martin
    Biochemistry and Molecular Biology, Augusta University, Augusta, Georgia, United States
  • Yuqing Huo
    Vascular Biology Center, Augusta University, Augusta, Georgia, United States
  • Manuela Bartoli
    Ophthalmology, Augusta University, Augusta, Georgia, United States
  • Footnotes
    Commercial Relationships   Albert Xiong None; Menaka Thounaojam None; Qiuhua Yang None; Ravirajsinh Jadeja None; Pamela Martin None; Yuqing Huo None; Manuela Bartoli None
  • Footnotes
    Support  EY028714
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 3050 – F0421. doi:
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    • Get Citation

      Albert Xiong, Menaka Thounaojam, Qiuhua Yang, Ravirajsinh Jadeja, Pamela M Martin, Yuqing Huo, Manuela Bartoli; Inhibition of miR-21 prevents abnormal angiogenesis and subretinal fibrosis in an experimental model of choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2022;63(7):3050 – F0421.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Choroidal neovascularization (CNV) and consequent sub-retinal fibrosis remain sight-threatening conditions with a significant percentage of patients being resistant to anti-VEGF-based treatments or presenting frequent recurrences. MicroRNA-21-5p (miR-21) is a non-coding RNA with pro-angiogenic and pro-fibrotic abilities that our group and others have previously studied for its pathogenic implications in diabetic and oxygen-induced retinopathy. Here, we have investigated the effects of blocking miR-21 in an experimental model of CNV.

Methods : CNV was induced in C57Bl/6J mice by laser injury of Bruch’s membrane and analyzed at different time points. MiR-21 inhibition was achieved by intraorbital injection of miR-21 Locked Nucleic Acid (LNA) inhibitor. As control, we used mice subjected to CNV that were injected with scramble antagomir or age-matched normal mice. Immunohistochemistry was performed to visualize retinal histopathological changes (hematoxilin/eosin staining) and to assess vascular density and distribution (isolectin B4), fibrotic progression (collagen I), and reactivity to alpha smooth muscle actin (alpha SMA) antibodies suggesting epithelial to mesenchymal transition (EMT). Quantitative RT-PCR was used to assess miR-21 levels in the different experimental groups.

Results : In untreated CNV mice neovascularization was observed to peak around day 14 post-injury before mildly regressing at day 21. Collagen I (Col1) staining showed that in CNV mice fibrosis progressed further beyond 14 days. In CNV mice treated with miR-21 inhibitor (a.miR-21), Col1 and Isolectin B4 stained areas were noticeably smaller beyond the 7-day post-injury time point as compared to untreated CNV mice or mice treated with scramble antagomir. Quantification of the fibrosed area through measurement of the Col1 stained areas in maximum projection images confirmed these findings. Expression of fibrosis and EMT markers (alpha SMA) were significantly downregulated in a.miR-21 injected mice. SD-OCT-based analysis also evidenced that a.miR-21 rescued retinal thickness and decreased neovascular lesions in CNV mice. Lastly, H&E staining confirmed improved retinal architecture in a.miR-21 treated CNV mice.

Conclusions : Our data indicate miR-21 as a novel player in CNV induction and progression and suggest its inhibition as a new therapeutic strategy for this potentially blinding condition.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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