Original article
Vitreous Levels of Angiopoietin-1 and Angiopoietin-2 in Eyes With Retinopathy of Prematurity

https://doi.org/10.1016/j.ajo.2010.08.037Get rights and content

Purpose

To determine the vitreous levels of angiopoietin (Ang)-1 and Ang-2 in eyes with retinopathy of prematurity (ROP), and to determine the correlation between the 2 levels.

Design

Retrospective case-control study.

Methods

Forty-eight eyes with stage 4 ROP were studied. Six eyes with congenital cataract were used as controls. The ROP eyes were classified by the vascular activity into highly (n = 22), moderately (n = 15), and mildly (n = 11) vascular-active ROP. Eyes with highly vascular-active ROP initially received 0.5 mg of intravitreal bevacizumab (IVB) and underwent vitrectomy within 1 week. The others underwent vitrectomy without IVB. Vitreous samples were collected at the beginning of vitrectomy, and the vitreous levels of Angs were measured by enzyme-linked immunosorbent assay.

Results

The mean concentrations of Ang-1 and Ang-2 were 201.9 and 7832.1 pg/mL in highly vascular-active ROP eyes, 216.1 and 7731.2 pg/mL in moderately vascular-active ROP eyes, 533.8 and 1685.9 pg/mL in mildly vascular-active ROP eyes, and 0 and 41.5 pg/mL in control eyes. The vitreous Ang-1 level was significantly higher (P < .05) in highly, moderately, and mildly vascular-active ROP eyes than in control eyes. The vitreous Ang-2 level was significantly higher (P < .05) in highly and moderately vascular-active ROP eyes than in control eyes. There was a significant negative correlation (r = −0.406; P = .040) between the Ang-1 and Ang-2 levels in moderately and mildly vascular-active ROP eyes.

Conclusions

The balance of Ang-1 and Ang-2 in the vitreous may be important in the pathogenesis of ROP.

Section snippets

Methods

Forty-eight eyes of 36 infants (17 female and 19 male infants) with stage 4 ROP (4A, 36 eyes; 4B, 12 eyes) were studied. The mean gestational age of the infants was 24.2 weeks (range, 22–26 weeks), and the mean birth weight was 640 grams (range, 332–977 grams). All of the infants underwent primary vitreous surgery at the Osaka University Hospital, Osaka, Japan from July 5, 2007 through December 24, 2009. All of the eyes underwent indirect photocoagulation of the avascular peripheral retina

Results

Among the eyes with stage 4 ROP, 22 eyes were classified as highly vascular-active ROP, 15 eyes as moderately vascular-active ROP, and 11 eyes as mildly vascular-active ROP. The mean vitreous level of Ang-1 was 201.9 pg/mL (range, 0 to 461.7 pg/mL) in the highly vascular-active ROP eyes, 216.1 pg/mL (range, 8.5 to 637.0 pg/mL) in the moderately vascular-active ROP eyes, 533.8 pg/mL (range, 218.9 to 1044.9 pg/mL) in the mildly vascular-active ROP eyes, and 0 pg/mL (range, 0 to 0 pg/mL) in the

Discussion

The major findings in this study are: first, the vitreous level of Ang-1 was significantly higher in the highly, moderately, and mildly vascular-active ROP eyes than in control eyes. Second, the vitreous Ang-2 level was significantly higher in the highly and moderately vascular-active ROP eyes than in control eyes. And third, there was a significant negative correlation between the Ang-1 and Ang-2 levels in the vitreous fluid of the moderately and mildly vascular-active ROP eyes.

Ang-1 was first

Tatsuhiko Sato, MD, received his medical degree from Osaka University Graduate School of Medicine, Suita, Japan, in 2001. He completed residency at Osaka University Hospital. Now he is an attending staff in Ophthalmology at Osaka Rosai Hospital. His field of interest includes surgical treatment of vitreoretinal disease such as diabetic retinopathy, retinal detachment, and retinopathy of prematurity.

References (27)

  • H. Mechoulam et al.

    Retinopathy of prematurity: molecular pathology and therapeutic strategies

    Am J Pharmacogenomics

    (2003)
  • K. Sonmez et al.

    vitreous levels of stromal cell-derived factor 1 and vascular endothelial growth factor in patients with retinopathy of prematurity

    Ophthalmology

    (2008)
  • H.A. Mintz-Hittner et al.

    Intravitreal injection of bevacizumab (avastin) for treatment of stage 3 retinopathy of prematurity in zone I or posterior zone II

    Retina

    (2008)
  • Cited by (37)

    • Retinopathy of prematurity: A review of pathophysiology and signaling pathways

      2023, Survey of Ophthalmology
      Citation Excerpt :

      Clinical studies and further research are needed to better elucidate the underlying molecular and cellular mechanisms that determine whether PLGF inhibition may have advantages over VEGF inhibition and, in clinical practice, whether or not they can be co-administered.385 Angiopoietins are growth factors that modulate physiological and pathological neovascularization particularly in association with VEGF.326 Ang-1 and Ang-2 are the most evaluated angiopoietins in preclinical studies.99

    • Dysregulated genomic and coding-transcriptomic factors in retinopathy of prematurity

      2022, Gene Reports
      Citation Excerpt :

      Ang1 amplifies the stability of vessels and vascular maturation, while Ang2 launches neovascularization (Umeda et al., 2003; Takagi et al., 2003). Ang2 levels were significantly increased in ROP patients (Banyasz et al., 2006; Sato et al., 2011). Due to the immature immune system of premature neonates, they are susceptible to infections and subsequent inflammation.

    • The Genetics of Retinopathy of Prematurity: A Model for Neovascular Retinal Disease

      2018, Ophthalmology Retina
      Citation Excerpt :

      EPO, a hormone known to stimulate red blood cell formation in bone marrow, and EPO receptors are expressed in the retina, and their expression is regulated by oxygen status.97,98 Mouse models of ROP have shown that vascular stability is affected by EPO levels, with exogenous restoration of EPO leading to a reduction in blood vessel dropout during the first phase of ROP.96 Conversely, elevated levels of EPO during the second stage of ROP exacerbated vasoproliferation, and the vitreous level of EPO is elevated in eyes with stage 4 ROP.

    • Pathophysiology, screening and treatment of ROP: A multi-disciplinary perspective

      2018, Progress in Retinal and Eye Research
      Citation Excerpt :

      Of these, in terms of retinal vascular development, the most important is VEGF. HIF-1α is also the master transcriptional regulator at a cellular level for numerous other genes that have a role in ROP, including erythropoitein (EPO) (Smith, 2008), angiopoietin 1 & 2 (Sato et al., 2011) and platelet-derived growth factor subunit B (PDGFB) (Wilkinson-Berka et al., 2004). Conversely, the presence of the mainly placental derived growth factor, insulin-like growth factor 1 (IGF-1), is essential for the regulation of HIF-1α protein synthesis; removing the neonate from the intrauterine environment can have potentially serious effects on HIF-1α expression, fetal development as a whole, and ultimately, normal retinal vascular development (Smith, 2008).

    View all citing articles on Scopus

    Tatsuhiko Sato, MD, received his medical degree from Osaka University Graduate School of Medicine, Suita, Japan, in 2001. He completed residency at Osaka University Hospital. Now he is an attending staff in Ophthalmology at Osaka Rosai Hospital. His field of interest includes surgical treatment of vitreoretinal disease such as diabetic retinopathy, retinal detachment, and retinopathy of prematurity.

    View full text