Modulation of Extracellular Matrix Composition and Chronic Inflammation with Pirfenidone Promotes Scar Reduction in Retinal Wound Repair
Wound repair in the retina is a complex mechanism, and a deeper understanding of it is necessary for the development of effective treatments to slow down or even prevent degenerative processes leading to photoreceptor loss. In this study, we harnessed a laser-induced retinal degeneration model (532-...
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| Format: | Article |
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MDPI AG
2024-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/13/2/164 |
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| author | Laura Jahnke Virginie Perrenoud Souska Zandi Yuebing Li Federica Maria Conedera Volker Enzmann |
| author_facet | Laura Jahnke Virginie Perrenoud Souska Zandi Yuebing Li Federica Maria Conedera Volker Enzmann |
| author_sort | Laura Jahnke |
| collection | DOAJ |
| description | Wound repair in the retina is a complex mechanism, and a deeper understanding of it is necessary for the development of effective treatments to slow down or even prevent degenerative processes leading to photoreceptor loss. In this study, we harnessed a laser-induced retinal degeneration model (532-nm laser photocoagulation with 300 μm spot size, 60 ms duration and 60 mV pulse), enabling a profound molecular elucidation and a comprehensive, prolonged observation of the wound healing sequence in a murine laser-induced degeneration model (C57BL/6J mice, 6–12 weeks) until day 49 post-laser. Our observations included the expression of specific extracellular matrix proteins and myofibroblast activity, along with an analysis of gene expression related to extracellular matrix and adhesion molecules through RNA measurements. Furthermore, the administration of pirfenidone (10 mg/kg via drinking water), an anti-inflammatory and anti-fibrotic compound, was used to modulate scar formation after laser treatment. Our data revealed upregulated collagen expression in late regenerative phases and sustained inflammation in the damaged tissue. Notably, treatment with pirfenidone was found to mitigate scar tissue formation, effectively downregulating collagen production and diminishing the presence of inflammatory markers. However, it did not lead to the regeneration of the photoreceptor layer. |
| first_indexed | 2024-03-08T09:55:45Z |
| format | Article |
| id | doaj.art-5a55306a5b1e4c1ba0f1671c2a88e4b5 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T09:55:45Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-5a55306a5b1e4c1ba0f1671c2a88e4b52024-01-29T13:50:29ZengMDPI AGCells2073-44092024-01-0113216410.3390/cells13020164Modulation of Extracellular Matrix Composition and Chronic Inflammation with Pirfenidone Promotes Scar Reduction in Retinal Wound RepairLaura Jahnke0Virginie Perrenoud1Souska Zandi2Yuebing Li3Federica Maria Conedera4Volker Enzmann5Department of Ophthalmology, Bern University Hospital, University of Bern, 3010 Bern, SwitzerlandDepartment of Ophthalmology, Bern University Hospital, University of Bern, 3010 Bern, SwitzerlandDepartment of Ophthalmology, Bern University Hospital, University of Bern, 3010 Bern, SwitzerlandDepartment of Ophthalmology, Bern University Hospital, University of Bern, 3010 Bern, SwitzerlandDepartment of Ophthalmology, Bern University Hospital, University of Bern, 3010 Bern, SwitzerlandDepartment of Ophthalmology, Bern University Hospital, University of Bern, 3010 Bern, SwitzerlandWound repair in the retina is a complex mechanism, and a deeper understanding of it is necessary for the development of effective treatments to slow down or even prevent degenerative processes leading to photoreceptor loss. In this study, we harnessed a laser-induced retinal degeneration model (532-nm laser photocoagulation with 300 μm spot size, 60 ms duration and 60 mV pulse), enabling a profound molecular elucidation and a comprehensive, prolonged observation of the wound healing sequence in a murine laser-induced degeneration model (C57BL/6J mice, 6–12 weeks) until day 49 post-laser. Our observations included the expression of specific extracellular matrix proteins and myofibroblast activity, along with an analysis of gene expression related to extracellular matrix and adhesion molecules through RNA measurements. Furthermore, the administration of pirfenidone (10 mg/kg via drinking water), an anti-inflammatory and anti-fibrotic compound, was used to modulate scar formation after laser treatment. Our data revealed upregulated collagen expression in late regenerative phases and sustained inflammation in the damaged tissue. Notably, treatment with pirfenidone was found to mitigate scar tissue formation, effectively downregulating collagen production and diminishing the presence of inflammatory markers. However, it did not lead to the regeneration of the photoreceptor layer.https://www.mdpi.com/2073-4409/13/2/164retina degenerationwound repairextracellular matrixpirfenidonefibrosisinflammation |
| spellingShingle | Laura Jahnke Virginie Perrenoud Souska Zandi Yuebing Li Federica Maria Conedera Volker Enzmann Modulation of Extracellular Matrix Composition and Chronic Inflammation with Pirfenidone Promotes Scar Reduction in Retinal Wound Repair Cells retina degeneration wound repair extracellular matrix pirfenidone fibrosis inflammation |
| title | Modulation of Extracellular Matrix Composition and Chronic Inflammation with Pirfenidone Promotes Scar Reduction in Retinal Wound Repair |
| title_full | Modulation of Extracellular Matrix Composition and Chronic Inflammation with Pirfenidone Promotes Scar Reduction in Retinal Wound Repair |
| title_fullStr | Modulation of Extracellular Matrix Composition and Chronic Inflammation with Pirfenidone Promotes Scar Reduction in Retinal Wound Repair |
| title_full_unstemmed | Modulation of Extracellular Matrix Composition and Chronic Inflammation with Pirfenidone Promotes Scar Reduction in Retinal Wound Repair |
| title_short | Modulation of Extracellular Matrix Composition and Chronic Inflammation with Pirfenidone Promotes Scar Reduction in Retinal Wound Repair |
| title_sort | modulation of extracellular matrix composition and chronic inflammation with pirfenidone promotes scar reduction in retinal wound repair |
| topic | retina degeneration wound repair extracellular matrix pirfenidone fibrosis inflammation |
| url | https://www.mdpi.com/2073-4409/13/2/164 |
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