MMP9 is involved in glycation end-products induced increase of retinal vascular permeability in rats and the therapeutic effect of minocycline.
OBJECTIVE
To determine the role of matrix metalloproteinase 9 (MMP9) in advanced glycation end-products (AGEs) induced damage to blood-retinal barrier (BRB) and the therapeutic effects of minocycline, an MMP inhibitor, against the BRB damages.


METHODS
Forty-eight Sprague Dawley rats were randomly assigned to 3 groups (16/group): A control group treated with bovine serum albumin (BSA), an AGE-BSA treated group, and a group treated with minocycline after AGE-BSA treatment. The retinas of all the animals were collected 2 weeks after treatment, and the levels of MMP9 protein and mRNA were detected by Western blotting, immunohistochemistry, and semi-quantitative RT-PCR. The permeability of retinal vessels was bio-assayed using the Evans Blue method. The correlation between the vessel permeability and the MMP9 protein levels was analyzed.


RESULTS
Compared with the BSA control group, the expression of retinal MMP9 mRNA and protein were significantly increased in the AGE-BSA group, and the retinal vascular permeability was also increased in the AGE-BSA group. After the minocycline treatment, the MMP9 expression was decreased sharply and the abnormal vascular permeability was improved. There was a significant correlation between the MMP9 expression and retinal vascular permeability.


CONCLUSIONS
MMP9 is involved in the AGE-induced retinal damage of vascular permeability, and the abnormal permeability can be partially reversed by treatment with minocycline.
Chen
Yong Dong
YD
Department of Ophthalmology, The First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
Xu
Xun
X
Xia
Xin
X
Wu
Haixiang
H
Liu
Kun
K
Zheng
Zhi
Z
Zhu
Dongqing
D
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology*; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D008833:Microcirculation / Q000187:drug effects; D008911:Minocycline / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D015854:Up-Regulation
D004338:Drug Combinations; D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D012710:Serum Albumin, Bovine; D020780:Matrix Metalloproteinase 9; D008911:Minocycline