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Article

PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H2O2-Injured Rat Model

1
Department of Biomedical Science, CHA University, Seongnam 13488, Korea
2
Research Institute of Placental Science, CHA University, Seongnam 13488, Korea
3
CHA Bundang Medical Center, Department of Ophthalmology, CHA University, Seongnam 13496, Korea
*
Author to whom correspondence should be addressed.
Academic Editors: Kunlin Jin, Huanxing Su and Guo-Yuan Yang
Cells 2021, 10(5), 1117; https://doi.org/10.3390/cells10051117
Received: 31 March 2021 / Revised: 3 May 2021 / Accepted: 4 May 2021 / Published: 6 May 2021
(This article belongs to the Special Issue Aging and Disease)
Retinal degenerative diseases result from oxidative stress and mitochondrial dysfunction, leading to the loss of visual acuity. Damaged retinal pigment epithelial (RPE) and photoreceptor cells undergo mitophagy. Pigment epithelium-derived factor (PEDF) protects from oxidative stress in RPE and improves mitochondrial functions. Overexpression of PEDF in placenta-derived mesenchymal stem cells (PD-MSCs; PD-MSCsPEDF) provides therapeutic effects in retinal degenerative diseases. Here, we investigated whether PD-MSCsPEDF restored the visual cycle through a mitophagic mechanism in RPE cells in hydrogen peroxide (H2O2)-injured rat retinas. Compared with naïve PD-MSCs, PD-MSCsPEDF augmented mitochondrial biogenesis and translation markers as well as mitochondrial respiratory states. In the H2O2-injured rat model, intravitreal administration of PD-MSCsPEDF restored total retinal layer thickness compared to that of naïve PD-MSCs. In particular, PTEN-induced kinase 1 (PINK1), which is the major mitophagy marker, exhibited increased expression in retinal layers and RPE cells after PD-MSCPEDF transplantation. Similarly, expression of the visual cycle enzyme retinol dehydrogenase 11 (RDH11) showed the same patterns as PINK1 levels, resulting in improved visual activity. Taken together, these findings suggest that PD-MSCsPEDF facilitate mitophagy and restore the loss of visual cycles in H2O2-injured rat retinas and RPE cells. These data indicate a new strategy for next-generation MSC-based treatment of retinal degenerative diseases. View Full-Text
Keywords: mitophagy; pigment epithelium-derived factor; placenta-derived mesenchymal stem cells; visual cycles; retinal degenerative diseases mitophagy; pigment epithelium-derived factor; placenta-derived mesenchymal stem cells; visual cycles; retinal degenerative diseases
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MDPI and ACS Style

Kim, J.Y.; Park, S.; Park, H.J.; Kim, S.H.; Lew, H.; Kim, G.J. PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H2O2-Injured Rat Model. Cells 2021, 10, 1117. https://doi.org/10.3390/cells10051117

AMA Style

Kim JY, Park S, Park HJ, Kim SH, Lew H, Kim GJ. PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H2O2-Injured Rat Model. Cells. 2021; 10(5):1117. https://doi.org/10.3390/cells10051117

Chicago/Turabian Style

Kim, Jae Y., Sohae Park, Hee J. Park, Se H. Kim, Helen Lew, and Gi J. Kim. 2021. "PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H2O2-Injured Rat Model" Cells 10, no. 5: 1117. https://doi.org/10.3390/cells10051117

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