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Ang‐2 upregulation correlates with increased levels of MMP‐9, VEGF, EPO and TGFβ1 in diabetic eyes undergoing vitrectomy
Author(s) -
Loukovaara Sirpa,
Robciuc Alexandra,
Holopainen Juha M.,
Lehti Kaisa,
Pessi Timo,
Liinamaa Johanna,
Kukkonen KirsiTiina,
Jauhiainen Matti,
Koli Katri,
KeskiOja Jorma,
Immonen Ilkka
Publication year - 2013
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2012.02473.x
Subject(s) - vitrectomy , downregulation and upregulation , vegf receptors , matrix metalloproteinase , ophthalmology , medicine , diabetic retinopathy , diabetes mellitus , endocrinology , visual acuity , chemistry , biochemistry , gene
. Purpose: Angiogenesis in diabetic retinopathy (DR) is a multifactorial process regulated by hypoxia‐induced growth factors and inflammatory cytokines. In addition to the angiogenic switch, the proteolytic processing and altered synthesis of the extracellular matrix are critical steps in this disease. This study was performed to evaluate the levels of matrix metalloproteinase‐2 and matrix metalloproteinase‐9 (MMP‐2 and MMP‐9), angiopoietin‐1 and angiopoietin‐2 (Ang‐1 and Ang‐2), vascular endothelial growth factor (VEGF), erythropoietin (EPO) and transforming growth factor‐β1 (totalTGFβ1) in the vitreous of diabetic eyes undergoing vitrectomy compared with control eyes operated because of macular hole or pucker. Methods: Prospective consecutive controlled observational study performed in the unit of vitreoretinal surgery in Finland during the years 2006–2008. Vitreous samples were collected before the start of the conventional 3‐ppp vitrectomy. Vitreous MMP‐2 and MMP‐9, Ang‐1 and Ang‐2, VEGF, EPO and TGFβ1 concentrations were measured from 69 patients with Type 1 or 2 diabetes and 40 controls. Results: Comparison of eyes with DR with controls revealed that the mean vitreous concentrations of proMMP‐2 (p = 0.0015), totalMMP‐2 (p = 0.0011), proMMP‐9 (p = 0.00001), totalMMP‐9 (p < 0.00001), Ang‐2 (p < 0.00001), VEGF (p < 0.00001), EPO (p < 0.00001) and totalTGFβ1 (p = 0.000026) were significantly higher in the former group. A multivariate logistic regression analysis suggested intravitreal Ang‐2 concentration being the key marker of PDR (p = 0.00025) (OR = 1507.9). Conclusion: The main new finding is that the intravitreal concentrations of Ang‐2 correlated significantly with MMP‐9, VEGF, EPO and TGFβ1 levels in diabetic eyes undergoing vitrectomy. Thus, these factors could promote retinal angiogenesis synergistically.