Plant-derived angiogenin fusion protein’s cytoprotective effect on trabecular meshwork damage induced by Benzalkonium chloride in mice

PeerJ

article

Jae Hoon Jeong¹  Soo Jin Lee⁴  Kisung Ko⁵  Jeong Hwan Lee⁵  Jungmook Lyu³  Moon Hyang Park⁷  Jaeku Kang²  Jae Chan Kim⁴ 

[1]Department of Ophthalmology, Konyang University Hospital

[2]Myunggok Medical Research Institute, Konyang University

[3]Myunggok Eye Research Institute, Konyang University

[4]Department of Ophthalmology, Chung-Ang University Hospital

[5]Therapeutic Protein Engineering Lab/College of Medicine, Chung-Ang University

[6]Department of Medical Science, Konyang University

[7]Department of Pathology, Konyang University Hospital

[8]Department of Pharmacology/College of Medicine, Konyang University

关键词: Angiongenin;    Benzalkonium chloride;    Biofarming;    Cytoprotection;    Trabecular meshwork;   

DOI  :  10.7717/peerj.9084

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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.

【 授权许可】

CC BY