May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
Purinergic Vasoprotection in Pericyte–Containing Retinal Microvessels
Author Affiliations & Notes
  • K. Shishida
    Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI
  • D.G. Puro
    Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI
  • Footnotes
    Commercial Relationships  K. Shishida, None; D.G. Puro, None.
  • Footnotes
    Support  NIH EY 12505, EY 07003, Research to Prevent Blindness
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 884. doi:
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      K. Shishida, D.G. Puro; Purinergic Vasoprotection in Pericyte–Containing Retinal Microvessels . Invest. Ophthalmol. Vis. Sci. 2006;47(13):884.

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

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Purpose: : In a number of pathophysiolgical conditions, including diabetic retinopathy, ischemia is likely to cause microvascular cell death and thereby, sight–threatening complications. Thus, identification of mechanisms that minimize cell death in ischemic retinal microvessels is of great interest. In this study, we tested the hypothesis that extracellular ATP, which is a putative vasoactive signal in the retinal microvasculature, can also play a protective role during ischemia.

Methods: : Complexes of pericyte–containing microvessels were isolated from papain–treated rat retinas. In our models of ischemia, the freshly isolated retinal microvessels were exposed either (1) to iodoacetate and antimycin A, which are inhibitors of ATP synthesis, or (2) to a glucose–free solution that had been bubbled for 15 min with 100% nitrogen. Cell viability was assayed by trypan blue dye exclusion.

Results: : We found that extracellular ATP diminished ischemia–induced cell death in pericyte–containing retinal microvessels. This vasoprotection occurred in a dose–dependent manner (IC50 = 150 µM). Exposure to extracellular ATP prior to the onset of ischemia reduced microvascular cell death by ∼80% (P < 0.001). However, this nucleotide also significantly (P = 0.019) diminished cell death when administered after periods of up to 5 hours of severe ischemia. Based on suramin and reactive blue–2 significantly (P < 0.001) blocking the vasoprotective effect of extracellular ATP, it appears that P2 purinergic receptors play a critical role in preventing ischemic cell death in microvessels of the retina.

Conclusions: : Extracellular ATP markedly reduces the vulnerability of pericyte–containing retinal microvessels to damage caused by profound ischemia.

Keywords: ischemia • vascular cells • retina 

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