Systemic treatment with a 5HT1a agonist induces anti-oxidant protection and preserves the retina from mitochondrial oxidative stress

Experimental Eye Research
Manas R BiswalAlfred S Lewin

Abstract

Chronic oxidative stress contributes to age related diseases including age related macular degeneration (AMD). Earlier work showed that the 5-hydroxy-tryptamine 1a (5HT1a) receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) protects retinal pigment epithelium (RPE) cells from hydrogen peroxide treatment and mouse retinas from oxidative insults including light injury. In our current experiments, RPE derived cells subjected to mitochondrial oxidative stress were protected from cell death by the up-regulation of anti-oxidant enzymes and of the metal ion chaperone metallothionein. Differentiated RPE cells were resistant to oxidative stress, and the expression of genes for protective proteins was highly increased by oxidative stress plus drug treatment. In mice treated with 8-OH-DPAT, the same genes (MT1, HO1, NqO1, Cat, Sod1) were induced in the neural retina, but the drug did not affect the expression of Sod2, the gene for manganese superoxide dismutase. We used a mouse strain deleted for Sod2 in the RPE to accelerate age-related oxidative stress in the retina and to test the impact of 8-OH-DPAT on the photoreceptor and RPE degeneration developed in these mice. Treatment of mice with daily injections of the drug l...Continue Reading

References

Apr 28, 1999·Free Radical Biology & Medicine·D J TateD A Newsome
Oct 23, 2002·Proceedings of the National Academy of Sciences of the United States of America·John W CrabbJoe G Hollyfield
Jan 28, 2004·Investigative Ophthalmology & Visual Science·Tracey A BaileyMichael E Cheetham
Dec 15, 2004·The Journal of Experimental Medicine·Emeline F NandrotSilvia C Finnemann
Oct 21, 2005·The Biochemical Journal·Sarah K BairdUlf T Brunk
Apr 8, 2006·The Lancet Oncology·Ed Susman
Jul 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·Yutaka ImamuraKazuo Tsubota
Feb 7, 2007·American Journal of Ophthalmology·Alejandra DecaniniTimothy W Olsen
Feb 9, 2007·Journal of Neurochemistry·Daniel S Cowen
Mar 29, 2007·The Journal of Biological Chemistry·Pablo R CastelloManisha Patel
Sep 28, 2007·Investigative Ophthalmology & Visual Science·Verline JustilienAlfred S Lewin
Oct 19, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shannon Reagan-ShawNihal Ahmad
Nov 28, 2007·The Journal of Biological Chemistry·Helena M Cochemé, Michael P Murphy
Jan 29, 2008·Nature Medicine·Joe G HollyfieldVictor L Perez
Mar 11, 2008·Investigative Ophthalmology & Visual Science·Majda HadziahmetovicJoshua L Dunaief
Mar 11, 2008·Investigative Ophthalmology & Visual Science·Yun-Zheng LeMeili Zhu
Aug 23, 2008·Antioxidants & Redox Signaling·Marcus J CalkinsJeffrey A Johnson
Nov 23, 2010·Investigative Ophthalmology & Visual Science·Robert J CollierCarmelo Romano
Apr 7, 2011·Investigative Ophthalmology & Visual Science·Robert J CollierCarmelo Romano
May 12, 2011·PloS One·Zhenyang ZhaoJiyang Cai
Oct 1, 2011·Investigative Ophthalmology & Visual Science·Zsolt AblonczyCraig E Crosson
Apr 19, 2012·Molecular Aspects of Medicine·Stuart G Jarrett, Michael E Boulton
Jun 23, 2012·Experimental Eye Research·Cynthia Xin-Zhao WangRafael L Ufret-Vincenty
Apr 24, 2014·Ophthalmology·Giovanni StaurenghiUNKNOWN International Nomenclature for Optical Coherence Tomography (IN•OCT) Panel
Apr 30, 2014·Investigative Ophthalmology & Visual Science·Cheryl L Rowe-RendlemanHenry F Edelhauser
Jul 6, 2014·Investigative Ophthalmology & Visual Science·Haoyu MaoAlfred S Lewin
Nov 27, 2014·AAPS PharmSciTech·Kishore CholkarAshim K Mitra

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Citations

Nov 20, 2018·Investigative Ophthalmology & Visual Science·Michael T MassengillAlfred S Lewin
May 17, 2017·Proceedings of the National Academy of Sciences of the United States of America·Sheldon RowanAllen Taylor
Aug 15, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Manas R BiswalJanet C Blanks
Mar 30, 2019·Investigative Ophthalmology & Visual Science·Dan JiangMark E Pennesi
Jan 15, 2021·Antioxidants·Ana Álvarez-BarriosHéctor González-Iglesias
Nov 13, 2018·Biochimie·Justine Masson
Jul 8, 2021·Translational Vision Science & Technology·Marco H JiEdward H Wood
Sep 15, 2021·Journal of Neurochemistry·Urszula KozlowskaMaciej Figiel

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