Matrix Metalloproteinases MMP-2 and MMP-9, Their Inhibitors TIMP-1 and TIMP-2, Vascular Endothelial Growth Factor and sVEGFR-2 as Predictive Markers of Ischemic Retinopathy in Patients with Systemic Sclerosis-Case Series Report

Int J Mol Sci. 2020 Nov 18;21(22):8703. doi: 10.3390/ijms21228703.


Systemic sclerosis (SSc) is an autoimmune connective tissue disorder associated with multiple organ involvement. The aim of the study was to present two SSc patients who were diagnosed with ischemic retinopathy in both eyes. As a background to our case study, we decided to investigate the imbalance of angiogenesis factors in 25 SSc patients in relation to 25 healthy controls. Assays of matrix metalloproteinases-2 and -9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1) and -2 (TIMP-2), vascular endothelial growth factor (VEGF), and soluble VEGF receptor-2 (sVEGFR-2) in blood serum and tears were performed. A significantly increased levels of MMP-9 in serum and tears, (p = 0.0375 and p < 0.001, respectively) as well as VEGF/sVEGFR-2 ratio in tears (p < 0.001) were found in the whole SSc patients group compared with controls, while reduced levels of these parameters in patients with ischemic sclerodermic retinopathy were noted. We also observed decreased level MMP-2 in tears and increased levels of TIMP-2 in blood serum and tears of SSc patients with retinal ischemic changes. MMP-9, MMP-2, TIMP-2, and VEGF/sVEGFR-2 may play a crucial role in ischemic retinal degeneration or retinal reorganization in SSc.

Keywords: MMP-2; MMP-9; TIMP-1; TIMP-2; VEGF; angiogenesis; ischemic retinopathy; sVEGFR-2; scleroderma.

Publication types

  • Case Reports

MeSH terms

  • Biomarkers / metabolism
  • Female
  • Humans
  • Ischemia* / complications
  • Ischemia* / metabolism
  • Ischemia* / pathology
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Retinal Diseases* / complications
  • Retinal Diseases* / metabolism
  • Retinal Diseases* / pathology
  • Scleroderma, Systemic* / complications
  • Scleroderma, Systemic* / metabolism
  • Scleroderma, Systemic* / pathology
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism*
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism*


  • Biomarkers
  • TIMP1 protein, human
  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Tissue Inhibitor of Metalloproteinase-2
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9