April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Up-regulation Of The Endothelin System In A Mouse Model Of Retinopathy Of Prematurity
Author Affiliations & Notes
  • Chintan Patel
    Vascular Biology Center,
    Georgia Health Sciences University, Augusta, Georgia
  • Wenbo Zhang
    Pharmacology & Toxicology,
    Georgia Health Sciences University, Augusta, Georgia
  • Modesto Rojas
    Vascular Biology Center,
    Georgia Health Sciences University, Augusta, Georgia
  • Zhimin Xu
    Vascular Biology Center,
    Georgia Health Sciences University, Augusta, Georgia
  • Steven E. Brooks
    Vascular Biology Center & VDI,
    Georgia Health Sciences University, Augusta, Georgia
  • R. W. Caldwell
    Pharmacology & Toxicology,
    Georgia Health Sciences University, Augusta, Georgia
  • Ruth B. Caldwell
    Vascular Biology Center,
    Georgia Health Sciences University, Augusta, Georgia
    VA Medical Center, Augusta, Georgia
  • Footnotes
    Commercial Relationships  Chintan Patel, None; Wenbo Zhang, None; Modesto Rojas, None; Zhimin Xu, None; Steven E. Brooks, None; R. W. Caldwell, None; Ruth B. Caldwell, None
  • Footnotes
    Support  Supported by GHSU Vision Discovery Institute, NIH Grants EY11766, EY04618, HL70215, VA Merit Award, JDRF 10-2009-575
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3990. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Chintan Patel, Wenbo Zhang, Modesto Rojas, Zhimin Xu, Steven E. Brooks, R. W. Caldwell, Ruth B. Caldwell; Up-regulation Of The Endothelin System In A Mouse Model Of Retinopathy Of Prematurity. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3990.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: : Retinopathy of prematurity (ROP) is a potentially blinding disease that affects preterm babies. ROP is thought to occur due to relative hyperoxia of the extra-uterine environment. This results in constriction and obliteration of the immature vessels, leading to retinal ischemia and vitreo-retinal neovascularization (VR-NV). The endothelin (ET) system is reported to be activated by ischemia in other tissues. Components of the ET system include the vasoactive ET peptides and their receptors ETA and ETB. ET-1 and 2 and ETA and B are present in retinal blood vessels, photoreceptors and glial cells. Activation of the retinal ET system has been reported following light-induced injury and retinal detachment. In this study, we tested the hypothesis that the ET system is activated in a mouse model of ROP.

Methods: : Mice were exposed to 75% oxygen from postnatal day P7 to P12, returned to room air from P12-P17, followed by hyperoxia-treatment (HT) before or after the onset of VR-NV, which reverses VR-NV and promotes vascular repair (Brooks et al., ARVO, 2011). A gene array analysis was performed using retinas of oxygen-induced retinopathy (OIR) and control mice at P17. Results were verified by using quantitative PCR and immunohistochemistry.

Results: : A whole genome array analysis revealed that the expression of 636 genes was significantly up-regulated while 138 genes was down-regulated. Amongst the up-regulated genes, the fold change of ET-2 and ETA receptor mRNA was the most prominent. This change was confirmed by quantitative PCR analysis, which revealed a large increase in mRNA of ET-2 (~370 fold) as well as a significant increase of ET-1 (~2 fold) and ETA receptor (~3 fold) in the retinas of OIR mice at P17 compared to the age-matched control mice. These expression levels were normalized by the HT. Similarly, a time-dependent increase of mRNA of ET-1, 2 and ETA receptor was also observed in OIR retinas from P12-P17. Further immunohistochemical analysis showed significant increases in ETA receptor protein expression in the OIR retinas. ETA was distributed across all layers of the retina and co-localized with blood vessels, astrocytes and Muller cells. In control mice, ETA was expressed mainly in outer nuclear layer.

Conclusions: : ET-2 and ETA are both strongly expressed in retinas of the mouse model of ROP and expression of these genes is completely normalized by HT. Activation of the ETA receptor may cause retinal vascular injury, glial cell activation and VR-NV during ROP. Hence, blockade of the ETA receptor may prove to be an effective therapy for ROP.

Keywords: retinopathy of prematurity • glia • gene microarray 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×