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Expression of matrix metalloproteinases and their inhibitors in experimental retinal ischemia-reperfusion injury in rats.
Exp Eye Res. 2002 May; 74(5):577-84.EE

Abstract

Matrix metalloproteinases (MMPs) are endopeptidases that degrade the extracellular matrix (ECM) and are involved in the pathogenesis of retinal degeneration along with tissue inhibitors of metalloproteinases (TIMPs). The present study examined the expression and activation of two specific members of MMPs (MMP-2 and MMP-9) and their related inhibitors (TIMP-1 and TIMP-2) in an experimental retinal ischemia-reperfusion injury. Retinal ischemia-reperfusion injury (RIRI) was induced in adult rats with a ligation method. After one hour of ischemia and a varied reperfusion time (0, 3, 6, 12, 24, 48 and 76 hr), the rat eyes were enucleated. Retinal extracts underwent zymographic analysis to measure the activity of MMP-2/9. The activity of TIMP-1 and TIMP-2 was measured by reverse zymography. The protein level was examined by Western blot. Immunohistochemistry analysis was undertaken to assess the anatomical distribution of MMP-9 in the retina after RIRI. The gelatinolytic activity of ProMMP-2 (72 kDa) was increased markedly at 6 hr after RIRI. ProMMP-9 (92 kDa) was not detected in the control specimens, while it appeared at 3 hr, increased markedly at 6 hr, and reached maximal levels at 24 hr after RIRI. The gelatinolytic activity found ian retinal extracts was shown to be inhibited by 10 m M EDTA and activated in vitro by a known metalloproteinase activator (4-aminophenylmercuric acetate (APMA)), indicating that these enzymes were of the metalloproteinase class. By western blot, MMP-2/9 levels increased parallel to protein activity level in zymography. No corresponding increase in TIMP-1 and TIMP-2 protein activity and protein level was detected by reverse zymography and western blot. Elevated levels of MMP-9 and its distribution in retina were confirmed by immunohistochemistry. Expression of MMP-9 was detected in the inner and outer segments of rat retina, and the level becomes stronger at 24 hr after RIRI. In this study, ProMMP-2 and ProMMP-9 were expressed and increased significantly, but their inhibitors (TIMP-1 and TIMP-2) remained relatively unaltered in ischemic retina after RIRI in rats. These results suggest that MMP-2 and MMP-9 may play an important role in the pathomechanism of retinal ischemic injury.

Authors+Show Affiliations

Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12076079

Citation

Zhang, Xu, et al. "Expression of Matrix Metalloproteinases and Their Inhibitors in Experimental Retinal Ischemia-reperfusion Injury in Rats." Experimental Eye Research, vol. 74, no. 5, 2002, pp. 577-84.
Zhang X, Sakamoto T, Hata Y, et al. Expression of matrix metalloproteinases and their inhibitors in experimental retinal ischemia-reperfusion injury in rats. Exp Eye Res. 2002;74(5):577-84.
Zhang, X., Sakamoto, T., Hata, Y., Kubota, T., Hisatomi, T., Murata, T., Ishibashi, T., & Inomata, H. (2002). Expression of matrix metalloproteinases and their inhibitors in experimental retinal ischemia-reperfusion injury in rats. Experimental Eye Research, 74(5), 577-84.
Zhang X, et al. Expression of Matrix Metalloproteinases and Their Inhibitors in Experimental Retinal Ischemia-reperfusion Injury in Rats. Exp Eye Res. 2002;74(5):577-84. PubMed PMID: 12076079.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of matrix metalloproteinases and their inhibitors in experimental retinal ischemia-reperfusion injury in rats. AU - Zhang,Xu, AU - Sakamoto,Taiji, AU - Hata,Yasuaki, AU - Kubota,Toshiaki, AU - Hisatomi,Toshio, AU - Murata,Toshinori, AU - Ishibashi,Tatsuro, AU - Inomata,Hajime, PY - 2002/6/22/pubmed PY - 2002/8/21/medline PY - 2002/6/22/entrez SP - 577 EP - 84 JF - Experimental eye research JO - Exp Eye Res VL - 74 IS - 5 N2 - Matrix metalloproteinases (MMPs) are endopeptidases that degrade the extracellular matrix (ECM) and are involved in the pathogenesis of retinal degeneration along with tissue inhibitors of metalloproteinases (TIMPs). The present study examined the expression and activation of two specific members of MMPs (MMP-2 and MMP-9) and their related inhibitors (TIMP-1 and TIMP-2) in an experimental retinal ischemia-reperfusion injury. Retinal ischemia-reperfusion injury (RIRI) was induced in adult rats with a ligation method. After one hour of ischemia and a varied reperfusion time (0, 3, 6, 12, 24, 48 and 76 hr), the rat eyes were enucleated. Retinal extracts underwent zymographic analysis to measure the activity of MMP-2/9. The activity of TIMP-1 and TIMP-2 was measured by reverse zymography. The protein level was examined by Western blot. Immunohistochemistry analysis was undertaken to assess the anatomical distribution of MMP-9 in the retina after RIRI. The gelatinolytic activity of ProMMP-2 (72 kDa) was increased markedly at 6 hr after RIRI. ProMMP-9 (92 kDa) was not detected in the control specimens, while it appeared at 3 hr, increased markedly at 6 hr, and reached maximal levels at 24 hr after RIRI. The gelatinolytic activity found ian retinal extracts was shown to be inhibited by 10 m M EDTA and activated in vitro by a known metalloproteinase activator (4-aminophenylmercuric acetate (APMA)), indicating that these enzymes were of the metalloproteinase class. By western blot, MMP-2/9 levels increased parallel to protein activity level in zymography. No corresponding increase in TIMP-1 and TIMP-2 protein activity and protein level was detected by reverse zymography and western blot. Elevated levels of MMP-9 and its distribution in retina were confirmed by immunohistochemistry. Expression of MMP-9 was detected in the inner and outer segments of rat retina, and the level becomes stronger at 24 hr after RIRI. In this study, ProMMP-2 and ProMMP-9 were expressed and increased significantly, but their inhibitors (TIMP-1 and TIMP-2) remained relatively unaltered in ischemic retina after RIRI in rats. These results suggest that MMP-2 and MMP-9 may play an important role in the pathomechanism of retinal ischemic injury. SN - 0014-4835 UR - https://www.unboundmedicine.com/medline/citation/12076079/Expression_of_matrix_metalloproteinases_and_their_inhibitors_in_experimental_retinal_ischemia_reperfusion_injury_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014483501911522 DB - PRIME DP - Unbound Medicine ER -