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LncRNA MALAT1 knockdown inhibits the development of choroidal neovascularization

Xiaoli Zhang1, Shu Du2, Defeng Yang3

  • 1Changchun Aier Eye Hospital, Aier Eye Hospital Group, Changchun, Nanguang District, Jilin Province, China.

Heliyon
|October 9, 2023
PubMed

Insights

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is upregulated in age-related macular degeneration. Inhibiting MALAT1 reduces choroidal neovascularization (CNV) and may offer a new therapeutic target for CNV.

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Genetics

Background:

  • Long non-coding RNAs (lncRNAs) are key regulators in age-related macular degeneration (AMD) pathogenesis.
  • Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is implicated in various cellular processes.

Purpose of the Study:

  • To investigate the role of MALAT1 in choroidal neovascularization (CNV) progression.
  • To elucidate the underlying molecular mechanisms of MALAT1 in CNV pathogenesis.

Main Methods:

  • Established in vivo (laser-induced mouse CNV model) and in vitro (hypoxia-exposed human choroidal vascular endothelial cells) CNV models.
  • Utilized small interference RNA (siRNA) to knockdown MALAT1 expression both in vivo and in vitro.
  • Analyzed MALAT1 expression, CNV development, leakage, and cell proliferation, migration, and tube formation.

Main Results:

  • MALAT1 expression was significantly upregulated in retinal pigment epithelial-choroidal complexes.
  • MALAT1 knockdown inhibited CNV development and leakage in vivo.
  • MALAT1 knockdown decreased human choroidal vascular endothelial cell proliferation, migration, and tube formation in vitro.
  • MALAT1 acted as a miR-17-5p sponge, regulating vascular endothelial growth factor A (VEGFA) and E26 transformation specific-1 (ETS1) expression.

Conclusions:

  • MALAT1 plays a critical role in the pathogenesis of CNV.
  • The MALAT1/miR-17-5p/VEGFA or ETS1 axis represents a potential therapeutic target for CNV treatment.
Keywords:
Choroidal neovascularization (CNV)Human choroidal vascular endothelial cells (HCVECs)HypoxiaMetastasis-associated lung adenocarcinoma transcript 1 (MALAT1)

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