The levels of hypoxia- and angiogenesis-related regulators and matrix metalloproteinase 9 activity in tear fluid of patients with non-penetrating ocular traumas

Abstract

This article was focused on the evaluation of protein biomarkers related to thrombosis, hypoxia, angiogenesis, and tissue remodeling in tear fluid of patients with non-penetrating corneal trauma. 32 patients with non-penetrating corneal injures were enrolled in the study, the control group consisted of 15 healthy patients. Samples of tear fluid were collected from the patients and control volunteers with the use of a disposable end micropipette. Protein levels of D-dimer, hypoxia-inducible factor 1α (HIF-1α), angiostatins, and matrix metalloproteinase 9 (MMP-9) in tear fluids were determined by western blot analysis. Proteolytic activity values of MMP-9 were measured by gelatin zymography. Results of western blot and zymography assay were calculated by densitometry analysis and expressed as arbitrary units. Significant increase of D-dimer and HIF-1α levels in tear fluid of patients with injured cornea by 7.3 (p<0.05) and 56 (p<0.001) folds, respectively was shown, compared with control, indicating thrombotic events and hypoxia condition to be involved in pathogenesis of ocular trauma. Dramatically elevated levels/activity of MMP-9 enzyme (by 105 folds vs. control, p<0.001) suggests intense tissue remodeling and degradation of extracellular matrix in the damaged cornea. Up-regulation of angiostatin level, products of proteolytical cleavage of plasminogen, in tear fluid collected from patients with traumatic eye in comparison with healthy volunteers (by 7.3 folds, p<0.05), could represent an adaptive mechanism, which counteracts excessive hypoxia-induced neovascularization of injured cornea. It is summarized that there was a strong association between elevation of D-dimer, HIF-1α, angiostatins, and MMP-9 levels suggesting thrombosis- and hypoxia-mediated mechanisms triggering wound healing of injured cornea. The findings of this study are novel and provide a basis for further investigations of the reparation mechanisms during non-penetrating ocular trauma. Studied proteins of tear fluid can serve as relevant biomarkers of corneal wound healing and are appropriate for diagnostic and prognostic purposes.

Angiostatins modulate ACE2 and GFAP levels in injured rat cornea and do not affect viability of retinal pigment epithelial cells

“…AS are abundantly produced in inflamed and vascularized corneas of experimental animals and play a vital role in regression of excessive neovascularization [11]. Currently, we have found that human tear fluid collected from the eye after non-penetrating corneal injury contains higher concentrations of AS than that of the healthy eye [33]. One of the most intriguing observations made in the present study is the AS-mediated down-regulation of ACE2 in alkali-burned rat cornea.…”

lectroacupuncture stimulation at CV4 sites prevents breast cancer-induced osteoporosis by activating the Wnt/β-catenin signaling pathway

“…c-src is known to play a role in bone resorption by regulating osteoclast activity [12]. CtSK is involved in the resorption of calcified cartilage during endochondral bone formation [13], and MMP9 is associated with tissue remodeling, wound healing and angiogenesis [14]. Based on these findings, it might be reasonable to conclude that EA stimulation at the CV4 site can effectively prevent bone loss in the context of breast cancerinduced osteoporosis.…”