Plant-derived angiogenin fusion protein’s cytoprotective effect on trabecular meshwork damage induced by Benzalkonium chloride in mice
Background Benzalkonium chloride (BAK), commonly used in glaucoma treatment, is an eye drop preservative with dose-dependent toxicity. Previous studies have observed the multi-functional benefits of angiogenin (ANG) against glaucoma. In our study, we evaluated ANG’s cytoprotective effect on the trab...
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PeerJ Inc.
2020-05-01
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| author | Jae Hoon Jeong Soo Jin Lee Kisung Ko Jeong Hwan Lee Jungmook Lyu Moon Hyang Park Jaeku Kang Jae Chan Kim |
| author_facet | Jae Hoon Jeong Soo Jin Lee Kisung Ko Jeong Hwan Lee Jungmook Lyu Moon Hyang Park Jaeku Kang Jae Chan Kim |
| author_sort | Jae Hoon Jeong |
| collection | DOAJ |
| description | Background Benzalkonium chloride (BAK), commonly used in glaucoma treatment, is an eye drop preservative with dose-dependent toxicity. Previous studies have observed the multi-functional benefits of angiogenin (ANG) against glaucoma. In our study, we evaluated ANG’s cytoprotective effect on the trabecular meshwork (TM) damage induced by BAK. Additionally, we developed a plant-derived ANG fusion protein and evaluated its effect on TM structure and function. Methods We synthesized plant-derived ANG (ANG-FcK) by fuzing immunoglobulin G’s Fc region and KDEL to conventional recombinant human ANG (Rh-ANG) purified from transgenic tobacco plants. We established a mouse model using BAK to look for degenerative changes in the TM, and to evaluate the protective effects of ANG-FcK and Rh-ANG. Intraocular pressure (IOP) was measured for 4 weeks and ultrastructural changes, deposition of fluorescent microbeads, type I and IV collagen, fibronectin, laminin and α-SMA expression were analyzed after the mice were euthanized. Results TM structural and functional degeneration were induced by 0.1% BAK instillation in mice. ANG co-treatment preserved TM outflow function, which we measured using IOP and a microbead tracer. ANG prevented phenotypic and ultrastructure changes, and that protective effect might be related to the anti-fibrosis mechanism. We observed a similar cytoprotective effect in the BAK-induced degenerative TM mouse model, suggesting that plant-derived ANG-FcK could be a promising glaucoma treatment. |
| first_indexed | 2024-03-09T07:00:53Z |
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| language | English |
| last_indexed | 2024-03-09T07:00:53Z |
| publishDate | 2020-05-01 |
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| spelling | doaj.art-33b07504c3ac4ca38723062ca6db0e122023-12-03T09:51:40ZengPeerJ Inc.PeerJ2167-83592020-05-018e908410.7717/peerj.9084Plant-derived angiogenin fusion protein’s cytoprotective effect on trabecular meshwork damage induced by Benzalkonium chloride in miceJae Hoon Jeong0Soo Jin Lee1Kisung Ko2Jeong Hwan Lee3Jungmook Lyu4Moon Hyang Park5Jaeku Kang6Jae Chan Kim7Department of Ophthalmology, Konyang University Hospital, Daejeon, South KoreaDepartment of Ophthalmology, Chung-Ang University Hospital, Seoul, South KoreaTherapeutic Protein Engineering Lab/College of Medicine, Chung-Ang University, Seoul, South KoreaTherapeutic Protein Engineering Lab/College of Medicine, Chung-Ang University, Seoul, South KoreaMyunggok Eye Research Institute, Konyang University, Daejeon, South KoreaDepartment of Pathology, Konyang University Hospital, Daejeon, South KoreaMyunggok Medical Research Institute, Konyang University, Daejeon, South KoreaDepartment of Ophthalmology, Chung-Ang University Hospital, Seoul, South KoreaBackground Benzalkonium chloride (BAK), commonly used in glaucoma treatment, is an eye drop preservative with dose-dependent toxicity. Previous studies have observed the multi-functional benefits of angiogenin (ANG) against glaucoma. In our study, we evaluated ANG’s cytoprotective effect on the trabecular meshwork (TM) damage induced by BAK. Additionally, we developed a plant-derived ANG fusion protein and evaluated its effect on TM structure and function. Methods We synthesized plant-derived ANG (ANG-FcK) by fuzing immunoglobulin G’s Fc region and KDEL to conventional recombinant human ANG (Rh-ANG) purified from transgenic tobacco plants. We established a mouse model using BAK to look for degenerative changes in the TM, and to evaluate the protective effects of ANG-FcK and Rh-ANG. Intraocular pressure (IOP) was measured for 4 weeks and ultrastructural changes, deposition of fluorescent microbeads, type I and IV collagen, fibronectin, laminin and α-SMA expression were analyzed after the mice were euthanized. Results TM structural and functional degeneration were induced by 0.1% BAK instillation in mice. ANG co-treatment preserved TM outflow function, which we measured using IOP and a microbead tracer. ANG prevented phenotypic and ultrastructure changes, and that protective effect might be related to the anti-fibrosis mechanism. We observed a similar cytoprotective effect in the BAK-induced degenerative TM mouse model, suggesting that plant-derived ANG-FcK could be a promising glaucoma treatment.https://peerj.com/articles/9084.pdfAngiongeninBenzalkonium chlorideBiofarmingCytoprotectionTrabecular meshwork |
| spellingShingle | Jae Hoon Jeong Soo Jin Lee Kisung Ko Jeong Hwan Lee Jungmook Lyu Moon Hyang Park Jaeku Kang Jae Chan Kim Plant-derived angiogenin fusion protein’s cytoprotective effect on trabecular meshwork damage induced by Benzalkonium chloride in mice PeerJ Angiongenin Benzalkonium chloride Biofarming Cytoprotection Trabecular meshwork |
| title | Plant-derived angiogenin fusion protein’s cytoprotective effect on trabecular meshwork damage induced by Benzalkonium chloride in mice |
| title_full | Plant-derived angiogenin fusion protein’s cytoprotective effect on trabecular meshwork damage induced by Benzalkonium chloride in mice |
| title_fullStr | Plant-derived angiogenin fusion protein’s cytoprotective effect on trabecular meshwork damage induced by Benzalkonium chloride in mice |
| title_full_unstemmed | Plant-derived angiogenin fusion protein’s cytoprotective effect on trabecular meshwork damage induced by Benzalkonium chloride in mice |
| title_short | Plant-derived angiogenin fusion protein’s cytoprotective effect on trabecular meshwork damage induced by Benzalkonium chloride in mice |
| title_sort | plant derived angiogenin fusion protein s cytoprotective effect on trabecular meshwork damage induced by benzalkonium chloride in mice |
| topic | Angiongenin Benzalkonium chloride Biofarming Cytoprotection Trabecular meshwork |
| url | https://peerj.com/articles/9084.pdf |
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