PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H<sub>2</sub>O<sub>2</sub>-Injured Rat Model
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 impro...
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MDPI AG
2021-05-01
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| author | Jae Yeon Kim Sohae Park Hee Jung Park Se Ho Kim Helen Lew Gi Jin Kim |
| author_facet | Jae Yeon Kim Sohae Park Hee Jung Park Se Ho Kim Helen Lew Gi Jin Kim |
| author_sort | Jae Yeon Kim |
| collection | DOAJ |
| description | 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-MSCs<sup>PEDF</sup>) provides therapeutic effects in retinal degenerative diseases. Here, we investigated whether PD-MSCs<sup>PEDF</sup> restored the visual cycle through a mitophagic mechanism in RPE cells in hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-injured rat retinas. Compared with naïve PD-MSCs, PD-MSCs<sup>PEDF</sup> augmented mitochondrial biogenesis and translation markers as well as mitochondrial respiratory states. In the H<sub>2</sub>O<sub>2</sub>-injured rat model, intravitreal administration of PD-MSCs<sup>PEDF</sup> 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-MSC<sup>PEDF</sup> 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-MSCs<sup>PEDF</sup> facilitate mitophagy and restore the loss of visual cycles in H<sub>2</sub>O<sub>2</sub>-injured rat retinas and RPE cells. These data indicate a new strategy for next-generation MSC-based treatment of retinal degenerative diseases. |
| first_indexed | 2024-03-10T11:40:09Z |
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| language | English |
| last_indexed | 2024-03-10T11:40:09Z |
| publishDate | 2021-05-01 |
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| spelling | doaj.art-13c5475bb7f34234bd5f8d3e0792043b2023-11-21T18:31:23ZengMDPI AGCells2073-44092021-05-01105111710.3390/cells10051117PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H<sub>2</sub>O<sub>2</sub>-Injured Rat ModelJae Yeon Kim0Sohae Park1Hee Jung Park2Se Ho Kim3Helen Lew4Gi Jin Kim5Department of Biomedical Science, CHA University, Seongnam 13488, KoreaDepartment of Biomedical Science, CHA University, Seongnam 13488, KoreaDepartment of Biomedical Science, CHA University, Seongnam 13488, KoreaDepartment of Biomedical Science, CHA University, Seongnam 13488, KoreaCHA Bundang Medical Center, Department of Ophthalmology, CHA University, Seongnam 13496, KoreaDepartment of Biomedical Science, CHA University, Seongnam 13488, KoreaRetinal 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-MSCs<sup>PEDF</sup>) provides therapeutic effects in retinal degenerative diseases. Here, we investigated whether PD-MSCs<sup>PEDF</sup> restored the visual cycle through a mitophagic mechanism in RPE cells in hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-injured rat retinas. Compared with naïve PD-MSCs, PD-MSCs<sup>PEDF</sup> augmented mitochondrial biogenesis and translation markers as well as mitochondrial respiratory states. In the H<sub>2</sub>O<sub>2</sub>-injured rat model, intravitreal administration of PD-MSCs<sup>PEDF</sup> 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-MSC<sup>PEDF</sup> 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-MSCs<sup>PEDF</sup> facilitate mitophagy and restore the loss of visual cycles in H<sub>2</sub>O<sub>2</sub>-injured rat retinas and RPE cells. These data indicate a new strategy for next-generation MSC-based treatment of retinal degenerative diseases.https://www.mdpi.com/2073-4409/10/5/1117mitophagypigment epithelium-derived factorplacenta-derived mesenchymal stem cellsvisual cyclesretinal degenerative diseases |
| spellingShingle | Jae Yeon Kim Sohae Park Hee Jung Park Se Ho Kim Helen Lew Gi Jin Kim PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H<sub>2</sub>O<sub>2</sub>-Injured Rat Model Cells mitophagy pigment epithelium-derived factor placenta-derived mesenchymal stem cells visual cycles retinal degenerative diseases |
| title | PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H<sub>2</sub>O<sub>2</sub>-Injured Rat Model |
| title_full | PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H<sub>2</sub>O<sub>2</sub>-Injured Rat Model |
| title_fullStr | PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H<sub>2</sub>O<sub>2</sub>-Injured Rat Model |
| title_full_unstemmed | PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H<sub>2</sub>O<sub>2</sub>-Injured Rat Model |
| title_short | PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H<sub>2</sub>O<sub>2</sub>-Injured Rat Model |
| title_sort | pedf mediated mitophagy triggers the visual cycle by enhancing mitochondrial functions in a h sub 2 sub o sub 2 sub injured rat model |
| topic | mitophagy pigment epithelium-derived factor placenta-derived mesenchymal stem cells visual cycles retinal degenerative diseases |
| url | https://www.mdpi.com/2073-4409/10/5/1117 |
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