Open AccessMatrix metalloproteinases-1, -13 and their tissue inhibitor-1 in endocrine ophthalmopathy
Author(s) -
E.S. Taskina,
S.V. Kharintseva
Publication year - 2019
Publication title -
problemy èndokrinologii
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.124
H-Index - 5
eISSN - 2308-1430
pISSN - 0375-9660
DOI - 10.14341/probl9750
Subject(s) - matrix metalloproteinase , extraocular muscles , graves' ophthalmopathy , extracellular matrix , medicine , endocrinology , hormone , endocrine system , thyroid , homeostasis , pathology , graves' disease , chemistry , ophthalmology , biochemistry
Effective regeneration of damaged soft orbital tissues in Graves ophthalmopathy (GO) requires coordinated remodeling of the extracellular matrix. Matrix metalloproteinases (MMPs) play an important role in the synthesis and degradation homeostasis of extracellular matrix components in various physiological and pathological conditions. Their proteolytic activity is inhibited by tissue inhibitors of metalloproteinases (TIMP). The biochemical processes taking place in extraocular muscles and retrobulbar tissue fibrogenesis in GO are not fully understood.
Aims to assess some biochemical mechanisms of extraocular muscles and retrobulbar tissue fibrogenesis in GO patients.
Material and methods. The study included 65 people (130 eyes) at the age of 43 (3550) years. Three groups of subjects were formed: 32 patients with a moderate GO severity (clinical group), 18 patients with autoimmune thyroid pathology without GO (comparison group), and 15 healthy persons (control). The diagnosis was based on clinical, laboratory, and instrumental data. A comprehensive ophthalmologic examination and blood sampling for determination of MMP-1, -13, TIMP-1, sulfated glycosaminoglycans (sGAG) and antibodies to thyroid-stimulating hormone receptor (TSHRAbs) were conducted. The data were statistically processed using the program Statistica 10.0.
Results. An elevated level of MMP-13, observed in all GO patients (p0.05). For the active phase of GOP, the comparison with the control group showed a 3.5-fold increase in MMP-13 (p0.001) and 1.17-fold rise in TIMP-1 (p0.05). Pulse glucocorticoid therapy reduced MMP-13 by 48.6% (p0.001), TIMP-1 by 2.7% (p0.001), and TSHRAbs by 93% (p0.001) compared with active GO, but these indicators were higher than the reference limits of control (p0.05). In inactive GO, despite increased MMP-13, TIMP-1 decreased to the reference values (p=0.533). There were no significant differences in MMP-1 in groups of subjects (p=0.865).
Conclusions. We have found imbalance between MMP-13 and TIMP-1 production in different activity phases of GO. Active GO is characterized by an increase in serum MMP-13 and TIMP-1. Dysregulation of intercellular matrix remodeling, possibly, underlies the development of extraocular muscles and retrobulbar tissue fibrosis in GO.