Purchase this article with an account.
Sirpa Loukovaara, Juha Holopainen, Alexandra Robciuc, Johanna M. Liinamaa, Kaisa Lehti, Jorma Keski-Oja, Ilkka J. Immonen; Ang-2 Upregulation Correlates With Increased Levels Of Mmp-9, Vegf, Epo And Tgf β1 In Vitrectomized Diabetic Eyes. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2878.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Angiogenesis in diabetic retinopathy is a multifactorial prosess 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 (ECM) are critical steps in this disease. This study was performed to evaluate the intravitreal profile of angiopoietin-1 and-2 (Ang-1 and -2), matrix metalloproteinase -2 and -9, vascular endothelial growth factor (VEGF), eythropoietin (EPO) and transforming growth factor-β1 (TGFβ1) in patients with diabetic retinopathy comparing the data with controls operated due to macular hole or quiescent pucker.
Prospective consecutive study performed in the unit of vitreoretinal surgery, Helsinki University Central Hospital in Finland during the years 2006-2008. Vitreous samples were collected before the start of the 3- ppp vitrectomy. Vitreous Ang-1, Ang-2, MMP-2, MMP-9, VEGF, EPO and TGFβ1 concentrations were measured from 109 human subjects: 69 patients with either Type 1 or 2 diabetic retinopathy, and 40 controls.
Comparision of eyes with DR with eyes operated due to macular hole or pucker revealed that the mean vitreous concentrations of Ang-2 (p<0.00001), proMMP-2 (p=0.0015), totalMMP-2 (p=0.0011), proMMP-9 (p=0.00001), totalMMP-9 (p<0.00001), VEGF (p<0.00001), EPO (p<0.00001) and totalTGFβ1 (p=0.000026) were all significantly higher in the former group.Subgroup analysis revealed that vitreous Ang-2 (p=0.0019), proMMP-9 (p=0.039), totalMMP-9 (p=0.021), VEGF (p=0.045), EPO (p=0.034) and TotalTGFβ1(p=0.0062) were higher in those diabetic eyes with tractional RD (n=23) compared to those without (n=44). Additionally, in active PDR subgroup (n=32), the mean levels of vitreous Ang-2 (p<0.00001), proMMP-9 (p=0.0003), totalMMP-9 (p=0.00001), VEGF (p=0.034), EPO (p=0.0002) and TotalTGFβ1(p=0.0003) were highest compared to the eyes with inactive PDR (n=35).In diabetic eyes, correlation analysis revealed a significant statistical correlation between the vitreous concentrations of Ang2 and proMMP-9 (r=0.70, p=0.000), total MMP-9 (r=0.66, p=0.000), VEGF (r=0.74, p=0.000), EPO (r=0.60, p=0.000) and totalTGF β1 (r=0.74, p=0.000).
The main new finding of this study is that in vitrectomized diabetic eyes the intravitreal concentrations of Ang-2 correlate highly significantly with MMP-9, VEGF, EPO and totalTGFβ1 levels. Thus, these markers seem to promote diabetic retinal angiogenesis synergestically.
Clinical Trial: :
Helsinki University Central Hospital, T1050SI601
This PDF is available to Subscribers Only