Pirfenidone Alleviates Choroidal Neovascular Fibrosis through TGF-β/Smad Signaling Pathway
Background. Transforming growth factor-β (TGF-β) plays a major role in CNV. However, the mechanism is unclear. This study investigates the effect of Pirfenidone (PFD) on TGF-β/Smad signaling pathway on the development of choroidal neovascular fibrosis in choroidal neovascularization (CNV) mouse mode...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Ophthalmology |
| Online Access: | http://dx.doi.org/10.1155/2021/8846708 |
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| author | Chuang Gao Xin Cao Lili Huang Yueqi Bao Tao Li Yue Di Liucheng Wu Yu Song |
| author_facet | Chuang Gao Xin Cao Lili Huang Yueqi Bao Tao Li Yue Di Liucheng Wu Yu Song |
| author_sort | Chuang Gao |
| collection | DOAJ |
| description | Background. Transforming growth factor-β (TGF-β) plays a major role in CNV. However, the mechanism is unclear. This study investigates the effect of Pirfenidone (PFD) on TGF-β/Smad signaling pathway on the development of choroidal neovascular fibrosis in choroidal neovascularization (CNV) mouse model. C57BL/6J male mice (aged from 6 to 8 weeks) received intravitreal injections of phosphate-buffered saline (PBS)/PFD solution on 14 days after laser injury. Mice were anesthetized by intraperitoneal injection of 4% pentobarbital (0.05 mg/g body weight). Optical Coherence Tomography (OCT), Fundus Fluorescein angiography (FFA), and hematoxylin-eosin (HE) were used to assess CNV formation. The fibrosis area was monitored by staining the collagen type I (Col-I). Western blotting was used to analyze the expression of TGF-β2, Smad 2/3, phosphorylated Smad 2/3 (p-Smad 2/3), and α-smooth muscle actin (α-SMA). Terminal deoxynucleotidy1 transferase dUTP nick-end labelling (TUNEL) assay was performed on cryosections of mouse eyes to detect apoptosis. Our data showed PFD inhibited areas of fibrosis during day 21 to day 28. We also found that the levels of TGF-β2 protein expressions increasingly reached the peak till the 3rd week during the CNV development. The protein levels of Smad 2/3, p-Smad 2/3, and α-SMA also increased significantly in CNV mice, but this response was profoundly suppressed by the TGF-β inhibitor PFD. The results of this study suggest that TGF-β2 represents a target to prevent or treat choroidal neovascular fibrosis, and PFD may provide an alternative to traditional methods for Wet Age-related macular degeneration (wAMD) treatment. |
| format | Article |
| id | doaj-art-9245a5d0708045d4a88760764f4a483c |
| institution | Kabale University |
| issn | 2090-004X 2090-0058 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Ophthalmology |
| spelling | doaj-art-9245a5d0708045d4a88760764f4a483c2025-02-03T01:29:21ZengWileyJournal of Ophthalmology2090-004X2090-00582021-01-01202110.1155/2021/88467088846708Pirfenidone Alleviates Choroidal Neovascular Fibrosis through TGF-β/Smad Signaling PathwayChuang Gao0Xin Cao1Lili Huang2Yueqi Bao3Tao Li4Yue Di5Liucheng Wu6Yu Song7Department of Ophthalmology, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226001, ChinaDepartment of Ophthalmology, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226001, ChinaDepartment of Ophthalmology, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226001, ChinaDepartment of Ophthalmology, Wuxi Children’s Hospital, Wuxi 214002, ChinaDepartment of Ophthalmology, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226001, ChinaDepartment of Ophthalmology, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226001, ChinaLaboratory Animal Center of Nantong University, Nantong, Jiangsu 226001, ChinaDepartment of Ophthalmology, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226001, ChinaBackground. Transforming growth factor-β (TGF-β) plays a major role in CNV. However, the mechanism is unclear. This study investigates the effect of Pirfenidone (PFD) on TGF-β/Smad signaling pathway on the development of choroidal neovascular fibrosis in choroidal neovascularization (CNV) mouse model. C57BL/6J male mice (aged from 6 to 8 weeks) received intravitreal injections of phosphate-buffered saline (PBS)/PFD solution on 14 days after laser injury. Mice were anesthetized by intraperitoneal injection of 4% pentobarbital (0.05 mg/g body weight). Optical Coherence Tomography (OCT), Fundus Fluorescein angiography (FFA), and hematoxylin-eosin (HE) were used to assess CNV formation. The fibrosis area was monitored by staining the collagen type I (Col-I). Western blotting was used to analyze the expression of TGF-β2, Smad 2/3, phosphorylated Smad 2/3 (p-Smad 2/3), and α-smooth muscle actin (α-SMA). Terminal deoxynucleotidy1 transferase dUTP nick-end labelling (TUNEL) assay was performed on cryosections of mouse eyes to detect apoptosis. Our data showed PFD inhibited areas of fibrosis during day 21 to day 28. We also found that the levels of TGF-β2 protein expressions increasingly reached the peak till the 3rd week during the CNV development. The protein levels of Smad 2/3, p-Smad 2/3, and α-SMA also increased significantly in CNV mice, but this response was profoundly suppressed by the TGF-β inhibitor PFD. The results of this study suggest that TGF-β2 represents a target to prevent or treat choroidal neovascular fibrosis, and PFD may provide an alternative to traditional methods for Wet Age-related macular degeneration (wAMD) treatment.http://dx.doi.org/10.1155/2021/8846708 |
| spellingShingle | Chuang Gao Xin Cao Lili Huang Yueqi Bao Tao Li Yue Di Liucheng Wu Yu Song Pirfenidone Alleviates Choroidal Neovascular Fibrosis through TGF-β/Smad Signaling Pathway Journal of Ophthalmology |
| title | Pirfenidone Alleviates Choroidal Neovascular Fibrosis through TGF-β/Smad Signaling Pathway |
| title_full | Pirfenidone Alleviates Choroidal Neovascular Fibrosis through TGF-β/Smad Signaling Pathway |
| title_fullStr | Pirfenidone Alleviates Choroidal Neovascular Fibrosis through TGF-β/Smad Signaling Pathway |
| title_full_unstemmed | Pirfenidone Alleviates Choroidal Neovascular Fibrosis through TGF-β/Smad Signaling Pathway |
| title_short | Pirfenidone Alleviates Choroidal Neovascular Fibrosis through TGF-β/Smad Signaling Pathway |
| title_sort | pirfenidone alleviates choroidal neovascular fibrosis through tgf β smad signaling pathway |
| url | http://dx.doi.org/10.1155/2021/8846708 |
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