miR‐184 regulates ezrin, LAMP‐1 expression, affects phagocytosis in human retinal pigment epithelium and is downregulated in age‐related macular degeneration
Open accessAbstract
MicroRNA 184 (miR‐184) is known to play a key role in neurological development and apoptosis and is highly expressed in mouse brain, mouse corneal epithelium, zebrafish lens and human retinal pigment epithelium (RPE). However, the role of miR‐184 in RPE is largely unknown. We investigated the role of miR‐184 in RPE and its possible implication in age‐related macular degeneration (AMD). Proteomic analysis identified the ezrin (EZR) gene as a target of miR‐184 in human RPE. EZR is a membrane cytoskeleton crosslinker that is also known to bind to lysosomal‐associated membrane protein 1 (LAMP‐1) during the formation of phagocytic vacuoles. In adult retinal pigment epithelium 19 (ARPE19) cells, inhibition of miR‐184 resulted in upregulation of EZR mRNA and EZR protein, and induced downregulation of LAMP‐1. The inhibition of miR‐184 decreased EZR‐bound LAMP‐1 protein levels and affected phagocytic activity in ARPE19 cells. In primary culture of human RPE isolated from eyes of AMD donors (AMD RPE), miR‐184 was significantly downregulated compared with control (normal) RPE. Downregulation of miR‐184 was consistent with significantly lower levels of LAMP‐1 protein in AMD RPE, and overexpression of MIR‐184 in AMD RPE was able to rescue LAMP‐1 protein expression to normal levels. Altogether, these observations suggest a novel role for miR‐184 in RPE health and support a model proposing that downregulation of miR‐184 expression during aging may result in dysregulation of RPE function, contributing to retinal degeneration.
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miR-184 expression is lower in RPE from AMD patients than healthy donors, leading to derepression of ezrin, which downregulates LAMP1, impairing phagocytosis and contributing to vision loss.
“Expression of miR-184 is lower in RPE from AMD patients than healthy donors. This lower level leads to derepression of its target, ezrin, which, in turn, downregulates lysosomal-associated membrane protein 1, impairing phagocytosis and contributing to vision loss [266].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [266]
The ‘miR-184 is downregulated in AMD’ section reports lower miR-184 in RPE from AMD donors. The Discussion (p. 5258) reports that inhibiting miR-184 increased ezrin, lowered LAMP-1, and reduced phagocytic activity in cultured RPE cells. But the paper could not detect an ezrin increase in AMD donor RPE, describes the proposed chain affecting phagocytosis as speculative, and does not establish that it contributes to vision loss. (LLM, conf=0.88)
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- Authors
- Murad, N., Kokkinaki, M., Gunawardena, N., Gunawan, M. S., Hathout, Y., Janczura, K. J., Theos, A. C., & Golestaneh, N.
- Affiliations
- Georgetown University Medical Center (US)
- Children's National (US)
- Corresponding author
- Golestaneh, Nady
- Venue
- The FEBS Journal
- Publisher
- Wiley
- Published
- 2014-10-13
- Volume
- 281
- Issue
- 23
- Pages
- 5251-5264
- ISSN
- 1742-464X (ISSN-L)
- 1742-4658
- OpenAlex
- W1991648357
- Cited by
- 73
- References
- 60
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 8 · 2022: 5 · 2021: 12 · 2020: 8 · 2019: 6 · 2018: 2 · 2017: 7 · 2016: 10 · 2015: 5
- FWCI
- 6.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Eye Institute
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- miR-184, microRNA, retinal pigment epithelium, age-related macular degeneration, ezrin, LAMP1, phagocytosis, lysosomal-associated membrane protein, ARPE-19 cells, retinal degeneration, miRNA target genes, cytoskeleton
- MeSH terms
- Ezrin, Adolescent, Aged, Aged, 80 and over, Cells, Cultured, Child, Cytoskeletal Proteins, Female, Humans, Macular Degeneration, Male, Middle Aged, Phagocytosis, Down-Regulation, MicroRNAs, Lysosomal Membrane Proteins, Lysosomal-Associated Membrane Protein 1, Retinal Pigment Epithelium, Retinal Photoreceptor Cell Outer Segment
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