May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Acute Retinal Ischemia/Reperfusion Causes Diabetic–like Capillary Degeneration That Is Inhibited by Pre–treatment With Aminoguanidine
Author Affiliations & Notes
  • L. Zheng
    Pharmacology,
    Case Western Reserve Univeristy, Cleveland, OH
  • T. Kern
    Ophthalmology,
    Case Western Reserve Univeristy, Cleveland, OH
  • Footnotes
    Commercial Relationships  L. Zheng, None; T. Kern, None.
  • Footnotes
    Support  EY00300
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 417. doi:
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      L. Zheng, T. Kern; Acute Retinal Ischemia/Reperfusion Causes Diabetic–like Capillary Degeneration That Is Inhibited by Pre–treatment With Aminoguanidine . Invest. Ophthalmol. Vis. Sci. 2005;46(13):417.

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

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Abstract

Abstract: : Purpose: Recent studies have been raised a possibly that vascular lesions in diabetic retinopathy might be mediated by factors released by surrounding nonvascular cells. To begin to explore this relationship, we studied (1) whether or not lesions generally believed to be neuronal, caused by acute increase in intraocular pressure (IOP), would cause vascular lesions, and (2) whether inhibition of iNOS, which has usually not been detected in retinal capillaries, could inhibit the vascular lesions. Methods: Ischemia–reperfusion injury to the retinas was induced in Lewis rats by elevating IOP (80–90 mmHg for 120 min), and reperfusion was established immediately afterward. Some rats were treated with aminoguanidine (50mg/Kg BW in drinking water) starting 2 days before the procedure. Poly(ADP–ribose) polymerase (PARP) activity and expression of ICAM–1, iNOS, COX–2 and PARP were measured by Western blot analysis or immunochemistry 2 days after the procedure. One week after elevated IOP, retinal blood vessels were isolated, and TUNEL and capillary degeneration were assessed. Caspase–3 activity was measured in whole retina homogenates and ganglion cells were counted in retinal sections. Results: Two days after increasing IOP, retinas showed PARP activation (detected by poly(ADP–ribosy)lated proteins), as well as up–regulation of ICAM–1, iNOS, COX–2 and PARP expression. After 1 week, there was increased caspase–3 activity and loss of ganglion cells, as expected. Interestingly, retinal vasculature had increased numbers of TUNEL positive cells and acellular capillaries. These lesions were morphologically similar to diabetic retinopathy in rats. Oral administration of aminoguanidine significantly inhibited the ischemia/reperfusion–induced capillary degeneration (as well as neural changes). Conclusions: Capillary degeneration is an unrecognized component of elevated IOP. A potent iNOS inhibitor, aminoguanidine, inhibited the capillary degeneration, even though iNOS has usually not been detected in the capillaries. Apparently, nonvascular cells such as nearby glia are releasing factors that lead to endothelial death. This IOP model offers new insight in the relationship between neuronal damage and vascular cell death in glaucoma and perhaps other disease like diabetic retinopathy.

Keywords: intraocular pressure • cell death/apoptosis • diabetic retinopathy 
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