Epac1 protects the retina against ischemia/reperfusion-induced neuronal and vascular damage

PloS One
Li LiuJena J Steinle

Abstract

We had previously reported that exchange protein for cAMP 1 (Epac1) reduced inflammatory mediators in the retina of mice and in retinal endothelial cells (REC). Since ischemia can induce retinal damage potentially through activation of inflammatory cascades, we hypothesized that Epac1 would protect the retina against neuronal and vascular damage after exposure to ischemia/reperfusion (I/R). We used Epac1 floxed and endothelial cell specific Epac1 knockout mice for this work. We exposed them to ischemia for 90 minutes followed by reperfusion. One day after I/R, some mice were used for fluorescein angiography imaging or Evan's blue measurements of permeability. Mice were sacrificed at 2 days for neuronal measurements and at 10 days for measurements of degenerate capillaries. Data show increased leakage in the Epac1 Cre-Lox (Epac1 EC-KO) mice exposed to I/R when compared to Epac1 floxed mice with the same treatment. I/R also increased numbers of degenerate capillaries and cell loss in all retinal layers of Epac1 EC-KO mice. Retinal thickness was reduced more significantly in the Epac1 EC-KO mice compared to Epac1 floxed mice after I/R. Taken together, the data suggest that Epac1 is protective against both neuronal and vascular dam...Continue Reading

References

Jun 18, 2010·Investigative Ophthalmology & Visual Science·Steven F AbcouwerDavid A Antonetti
Jul 14, 2010·Journal of Pediatric Surgery·Philip M TatumReed A Dimmitt
Aug 11, 2011·Investigative Ophthalmology & Visual Science·Galina DvoriantchikovaDmitry Ivanov
Dec 8, 2011·British Journal of Pharmacology·Euan ParnellStephen J Yarwood
Apr 3, 2012·Investigative Ophthalmology & Visual Science·Qiuhua ZhangJena J Steinle
Mar 26, 2013·Journal of Visualized Experiments : JoVE·Maria Radu, Jonathan Chernoff
Dec 12, 2013·Journal of Neuroinflammation·Steven F AbcouwerDavid A Antonetti
Aug 7, 2014·Investigative Ophthalmology & Visual Science·Yun QiXiaoxin Li
Jan 24, 2017·Investigative Ophthalmology & Visual Science·Youde JiangJena J Steinle
May 10, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Adam H KorayemWalter N Durán
Dec 21, 2017·International Journal of Ophthalmology·Yue-Lu ZhangLin Liu

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Citations

Jan 10, 2020·The Journal of Experimental Medicine·Wei LiuWenbo Zhang
Aug 6, 2020·International Journal of Molecular Sciences·Diana R GutsaevaManuela Bartoli

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Methods Mentioned

BETA
Genotyping
PCR

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