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

Jae Yeon Kim; Sohae Park; Hee Jung Park; Se Ho Kim; Helen Lew; Gi-Jin Kim

doi:10.3390/cells10051117

journal article Open Access May 06, 2021

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

Jae Yeon Kim

Sohae Park Hee Jung Park

Se Ho Kim

Helen Lew

Gi-Jin Kim

Cells Vol. 10 No. 5 pp. 1117 · MDPI AG

View at Publisher Save 10.3390/cells10051117

Abstract

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.

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Details

Published: May 06, 2021
Vol/Issue: 10(5)
Pages: 1117
License: View

Authors

J

Jae Yeon Kim

Department of Biomedical Science, CHA University, Seongnam 13488, Korea; Research Institute of Placental Science, CHA University, Seongnam 13488, Korea

S

Sohae Park

Department of Biomedical Science, CHA University, Seongnam 13488, Korea

H

Hee Jung Park

Department of Biomedical Science, CHA University, Seongnam 13488, Korea

S

Se Ho Kim

Department of Biomedical Science, CHA University, Seongnam 13488, Korea

H

Helen Lew

CHA Bundang Medical Center, Department of Ophthalmology, CHA University, Seongnam 13496, Korea

G

Gi-Jin Kim

Department of Biomedical Science, CHA University, Seongnam 13488, Korea; Research Institute of Placental Science, CHA University, Seongnam 13488, Korea

Funding

the National Research Foundation of Korea Award: 2019R111A1A01057255

Cite This Article

Jae Yeon Kim, Sohae Park, Hee Jung Park, et al. (2021). PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H2O2-Injured Rat Model. Cells, 10(5), 1117. https://doi.org/10.3390/cells10051117

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

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