Research of TIMP, MMP, CTGF, VEGF levels in aqueous humor and blood, in the eyes of patients, with and without pseudoexfoliation syndrome

Purpose: Etiopathogenesis of pseudoexfoliation syndrome (PES) which is commonly seen in our contry is stil controversial. In this study we aimed to determine if aqueous humor (AH) and serum levels of tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), matrix metalloproteinase 9 (MMP-9), connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF) differred between patients with PES and without PES, thus whether regulation of these substances might have a potential role in the treatment of PES.Materials and Methods: Seventy-two eyes of 72 patients (PES group n:30, control group without any other ocular pathology except cataract n:42) undergoing cataract surgery were included in the study. Patients with pseudoexfoliative glaucoma (PEG) were further considered as PEG+ subgroup and patients without glaucoma as PEG- subgroup. Blood specimens (5 ml) were collected on the day of cataract surgery from the forearm and AH samples from the anterior chamber (100 ?l ) during cataract surgery. Serum specimens obtained after centrifugation of blood samples and AH samples were stored in deep freezer until analysis. TIMP-1 and MMP-9 levels were determined in AH samples and TIMP-1, MMP-9, CTGF and VEGF levels were determined in serum samples using specific enzyme immunoassays (ELISA).Results: The mean MMP-9 and TIMP-1 AH levels were 3.54 ± 5.09 ng / ml and 31.2 ± 37.9 ng / ml in the PES group, and 21.1 ± 16.08 ng / ml and 31, 2 ± 37.9 ng / ml in the control group, respectively (p>0.05) . The mean serum levels of MMP-9 and TIMP-1 were 283.7 ± 348.6 ng / ml and 122.4 ± 150.3 in the PES group, and 427.4 ± 435.7 ng / ml and 97.5 ± 57.9 ng / ml in the control group, respectively (p>0.05). The mean VEGF and CTGF levels in serum samples were 333,08±241,73 ng/ml and 570,95±1222,13 ng/ml in the PES group, and 381,73±226,2 ng/ml and 449,48± 459,64 ng/ml, in the control group respectively (p>0.05). HA TIMP levels were significantly higher in PEG+ subgroup compared to PEG- subgroup (p=0.012), while HA MMP-9 levels were lower in PEG+ subgroup compared to PEG- subgroup (p>0.05). Mean serum TIMP-1 level was higher in PEG - subgroup compared to PEG+ subgroup , and mean serum MMP-9 level was lower in PEG+ subgroup compared to PEG- subgroup (p>0.005). Mean serum CTGF levels were higher in PEG+ subgroup compared to PEG- subgroup (p>0.005), while mean serum VEGF levels were very close in both subgroups (p>0.005).Conclusion: MMP-9, TIMP-1 and CTGF levels differ in PES patients from patients without PES in both AH and serum. This suppports that extracellular homeostasis is disturbed resulting in accumulation of extracellular matrix. The findings that patients with PEG had different levels of MMP-9, TIMP-1 and CTGF compared to PES patients without glaucoma make think that PEG is a more severe form of PES. It might be foreseen that development of preventive treatments in the future by regulation of interactions between MMP-9, TIMP-1 and CTGF will inhibit or slow down the progression of PES.Key Words: pseudoexfoliation syndrome, aqueous humor, extracellular matrix, MMP-9, TIMP-1, CTGF