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Apigenin Regulates Activation of Microglia and Counteracts Retinal Degeneration.
- Source :
-
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics [J Ocul Pharmacol Ther] 2020 Jun; Vol. 36 (5), pp. 311-319. Date of Electronic Publication: 2020 May 05. - Publication Year :
- 2020
-
Abstract
- Purpose: Photoreceptor degeneration is a major cause of blindness. Microglia are known to play key roles in the pathogenesis and progression of neural degeneration. We examined the possible use of apigenin, which is a naturally occurring flavonoid, for the treatment of photoreceptor degeneration through regulation of microglial activities. Methods: As in vitro analyses, BV2 and MG5 mouse microglia cell lines were stimulated in the presence or absence of apigenin, and their activation profile was examined. In vivo study was done using rd1 photoreceptor degeneration model, and apigenin was administered by intravitreal injection, and pathological feature was examined. Results: Cell survival was not affected by apigenin in either BV2 and MG5. Apigenin suppressed lipopolysaccharide (LPS)-induced chemokine production in both BV2 and MG5 cells, but phagocytosis was suppressed in MG5 cells but not in BV2 cells. Apigenin inhibited LPS-induced M1 activation but could not drive microglia toward the M2 phenotype. Apigenin suppressed the expression of miR-155 in a dose-dependent manner. Furthermore, the Ets protein level was suppressed by treatment of BV2 cells with apigenin. When rd1 mice were treated with apigenin by intravitreal injection, the expression of inflammatory chemokines in the retina was reduced, and activation of microglia and Müller glia was suppressed. Furthermore, the thickness of the outer nuclear layer of the retina of rd1 mice was thicker in apigenin-treated retinas. Conclusions: Taken together, local administration of apigenin to the retina is a potential therapeutic treatment for photoreceptor degeneration, which involves downregulation of microglia in the retina when photoreceptors are damaged.
- Subjects :
- Animals
Apigenin administration & dosage
Chemokines drug effects
Chemokines metabolism
Down-Regulation
Flavonoids administration & dosage
Intravitreal Injections methods
Lipopolysaccharides metabolism
Mice
MicroRNAs drug effects
MicroRNAs metabolism
Microglia metabolism
Models, Animal
Phagocytosis drug effects
Photoreceptor Cells, Vertebrate metabolism
Retina metabolism
Retinal Degeneration pathology
Apigenin pharmacology
Flavonoids pharmacology
Microglia drug effects
Photoreceptor Cells, Vertebrate drug effects
Retinal Degeneration drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1557-7732
- Volume :
- 36
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 32379991
- Full Text :
- https://doi.org/10.1089/jop.2019.0163