April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Inhibition of polyamine oxidase reduces hyperoxia-mediated retinal neuro-vascular injury in a model of retinopathy of prematurity
Author Affiliations & Notes
  • S. Priya Narayanan
    Vascular Biology Center, Georgia Regents University, Augusta, GA
    Vision Discovery Institute, Georgia Regents University, Augusta, GA
  • Zhimin Xu
    Vascular Biology Center, Georgia Regents University, Augusta, GA
    Vision Discovery Institute, Georgia Regents University, Augusta, GA
  • Tahira Lemtalsi
    Vascular Biology Center, Georgia Regents University, Augusta, GA
    Vision Discovery Institute, Georgia Regents University, Augusta, GA
  • Robert William Caldwell
    Vision Discovery Institute, Georgia Regents University, Augusta, GA
    Deapartment of Pharmacology and Toxicology, Georgia Regents University, Augusta, GA
  • Ruth B Caldwell
    Vascular Biology Center, Georgia Regents University, Augusta, GA
    VA medical center, Augusta, GA
  • Footnotes
    Commercial Relationships S. Priya Narayanan, None; Zhimin Xu, None; Tahira Lemtalsi, None; Robert William Caldwell, None; Ruth Caldwell, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1716. doi:https://doi.org/
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      S. Priya Narayanan, Zhimin Xu, Tahira Lemtalsi, Robert William Caldwell, Ruth B Caldwell; Inhibition of polyamine oxidase reduces hyperoxia-mediated retinal neuro-vascular injury in a model of retinopathy of prematurity. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1716. doi: https://doi.org/.

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

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Abstract

Purpose: Retinopathy of prematurity (ROP) is a potentially blinding eye disorder that affects infants born prematurely. It is one of the most common causes of vision loss in childhood and can lead to lifelong vision impairment and blindness. Using an oxygen-induced retinopathy (OIR) mouse model for ROP, we have shown that deletion of the arginase2 significantly reduces neuronal injury through the regulation of polyamine metabolism (Narayanan et al ARVO 2012).The present study was undertaken to determine whether inhibiting polyamine oxidase using MDL 72527 (N, N′-Bis (2, 3-butadienyl)-1, 4-butanediamine dihydrochloride) can reduce neuronal, glial and vascular injury in the OIR retina.

Methods: Newborn wild-type (WT) mice were used. Pups were exposed 70% oxygen from postnatal day 7 to 12, returned to room air, and were sacrificed at different stages of OIR. Pups were treated daily with MDL 72527 (39 mg/Kg of body weight, in saline, intraperitoneal). Vehicle groups received intraperitoneal injections of saline. Retinal cryostat sections were prepared for immunostaining analysis and TUNEL labeling of apoptotic cells. Analysis of vaso-obliteration was performed on retinal flatmounts. Fresh frozen retinal samples were used for Western blotting analysis.

Results: During the hyperoxic phase of OIR, a significant increase in the number of apoptotic cells was observed in the WT retina compared to normoxic controls. Treatment using MDL 72527 significantly reduced the number of TUNEL positive cells in the OIR retina compared to vehicle treated groups (p< 0.01, N=5). Immunolabeling studies using synaptophysin antibody showed the presence of improved synaptic contacts in MDL 72527-treated OIR retina compared to vehicle treated groups. Vaso-obliteration analyses using retinal flatmounts showed significantly reduced avascular area in MDL 72527-treated OIR retina compared to vehicle-treated (p< 0.05, N=6) retinas after 2 or 5 days of hyperoxia. Immunolabelling studies using Iba1 antibody demonstrated that activation of microglia was markedly reduced in MDL 72527-treated OIR retina. Studies on signaling pathways showed the involvement of JNK/SAPK pathway and cytochrome C in the polyamine oxidase mediated neuro-vascular injury during OIR treatment.

Conclusions: Our data suggest that polyamine oxidase is crucially involved in hyperoxia-induced neuro-vascular injury in the ROP retina.

Keywords: 706 retinopathy of prematurity • 615 neuroprotection • 714 signal transduction  
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