The activated form of gelatinase B/matrix metalloproteinase-9 is associated with diabetic vitreous hemorrhage.
We aimed to investigate the presence and activation status of matrix metalloproteinase (MMP)-2 and MMP-9 in vitreous samples from proliferative diabetic retinopathy (PDR) patients. Paired vitreous and serum samples were obtained from patients undergoing vitrectomy for the treatment of rhegmatogenous retinal detachment (RD) (65 patients) and PDR (67 patients). PDR patients were diagnosed for the presence of hemorrhage and/or patent new vessels. Quantitative assays were performed for vitreous protein content, MMP-2, MMP-9, tissue inhibitor of metalloproteinases-1 (TIMP-1) and hemoglobin. Qualitative evaluation of the MMP-2 and MMP-9 activation status was performed by zymography. Vitreous samples contained proMMP-2 but levels were unselectively related to total protein content. ProMMP-9 and activated MMP-9 levels were significantly increased in PDR patients (p<0.001 for both comparisons). In addition, TIMP-1 levels were significantly increased in PDR patients (p=0.004) and functionally inhibited activation of MMP-9 in vitreous samples. None of the parameters significantly differed between PDR patients with patent new vessels and those with inactive disease. However, activated MMP-9 levels in vitreous samples of PDR patients with hemorrhage (75.7+/-106.3 scanning units per 2 microl) were significantly higher than those in PDR patients without hemorrhage (7.1+/-16.2 scanning units per 2 microl) (p<0.001) and strongly correlated with hemoglobin levels (r=0.7525; p<0.001). Activated MMP-9 was not detected in paired serum samples. We conclude that activated MMP-9 might be involved in hemorrhagic transformation in patients with PDR.
Descamps
Francis J
FJ
Laboratory of Immunobiology, Rega Institute, University of Leuven, Belgium.
Martens
Erik
E
Kangave
Dustan
D
Struyf
Sofie
S
Geboes
Karel
K
Van Damme
Jo
J
Opdenakker
Ghislain
G
Abu El-Asrar
Ahmed M
AM
D017364:Collagenases / Q000032:analysis; D003930:Diabetic Retinopathy / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D004792:Enzyme Precursors / Q000032:analysis; D005136:Eye Proteins / Q000032:analysis; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D012163:Retinal Detachment / Q000201:enzymology / Q000378:metabolism; D015861:Retinal Neovascularization / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D014822:Vitreous Body / Q000737:chemistry; D014823:Vitreous Hemorrhage / Q000201:enzymology / Q000378:metabolism*
D004792:Enzyme Precursors; D005136:Eye Proteins; D006454:Hemoglobins; D019715:Tissue Inhibitor of Metalloproteinase-1; D017364:Collagenases; C120487:pro-matrix metalloproteinase 9; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9