| RRC ID |
88457
|
| 著者 |
Ando S, Hashida N, Yamashita D, Kawabata T, Asao K, Kawasaki S, Sakurai K, Yoshimori T, Nishida K.
|
| タイトル |
Rubicon regulates A2E-induced autophagy impairment in the retinal pigment epithelium implicated in the pathology of age-related macular degeneration.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
Waste product deposition and light stress in the retinal pigment epithelium (RPE) are crucial factors in the pathogenesis of various retinal degenerative diseases, including age-related macular degeneration (AMD), a leading cause of vision loss in elderly individuals worldwide. Given that autophagy in the RPE suppresses waste accumulation, determining the molecular mechanism by which autophagy is compromised in degeneration is necessary. Using polarized human RPE sheets, we found that bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E), a major toxic fluorophore of lipofuscin, causes significant impairment of autophagy and the simultaneous upregulation of Rubicon, a negative regulator of autophagy. Importantly, this impairment was reversed in Rubicon-specific siRNA-treated RPE sheets. In a retinal functional analysis using electroretinograms (ERGs), mice with the RPE-specific deletion of Rubicon showed no significant differences from control cre-expressing mice but presented partially but significantly enhanced amplitudes compared with Atg7 knockout mice. We also found that an inflammatory reaction in the retina in response to chronic blue light irradiation was alleviated in mice with the RPE-specific deletion of Rubicon. In summary, we propose that upregulating basal autophagy by targeting Rubicon is beneficial for protecting the RPE from functional damage with ageing and the inflammatory reaction caused by light-induced cellular stress.
|
| 巻・号 |
551
|
| ページ |
148-154
|
| 公開日 |
2021-4-30
|
| DOI |
10.1016/j.bbrc.2021.02.148
|
| PII |
S0006-291X(21)00380-6
|
| PMID |
33740621
|
| MeSH |
Aging / metabolism
Animals
Autophagy / drug effects*
Autophagy-Related Protein 7 / metabolism
Electroretinography
Female
Inflammation / metabolism
Intracellular Signaling Peptides and Proteins / deficiency
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism*
Lipofuscin / metabolism
Macular Degeneration / chemically induced
Macular Degeneration / metabolism*
Macular Degeneration / pathology*
Male
Mice
Mice, Inbred C57BL
Phagocytosis
Retinal Pigment Epithelium / drug effects*
Retinal Pigment Epithelium / metabolism
Retinal Pigment Epithelium / pathology*
Stress, Physiological / radiation effects
|
| リソース情報 |
| 実験動物マウス |
RBRC02759 |
