Intraocular DHODH-inhibitor PP-001 suppresses relapsing experimental uveitis and cytokine production of human lymphocytes, but not of RPE cells

Journal of Neuroinflammation
Maria Diedrichs-MöhringGerhild Wildner

Abstract

Uveitis is a potentially blinding inflammatory disease of the inner eye with a high unmet need for new therapeutic interventions. Here, we wanted to investigate the suppressive effect of the intraocular application of the small molecule dihydroorotate dehydrogenase (DHODH)-inhibitor PP-001 on experimental relapsing rat uveitis and furthermore determine its effect on proliferation and cytokine secretion of human peripheral blood lymphocytes (PBL) and human retinal pigment epithelial (RPE) cells in vitro. Spontaneously relapsing uveitis was induced in rats by immunization with interphotoreceptor retinoid-binding protein (IRBP) peptide R14. PP-001 was injected intravitreally after resolution of the primary disease to investigate further relapses. Proliferation and metabolic activity of phytohemagglutinin (PHA)-stimulated human peripheral lymphocytes with and without PP-001 and cytokine secretion were determined by XTT assay and bioplex bead assay. The RPE cell line ARPE-19 as well as primary human RPE cells treated with PP-001 or anti-vascular endothelial growth factor (VEGF) antibody bevacizumab were also investigated for metabolic activity and cytokine/chemokine secretion. Injection of PP-001 into rat eyes reduced the number of ...Continue Reading

References

Nov 1, 1987·The British Journal of Ophthalmology·E M GrahamM D Sanders
Oct 1, 1993·Journal of Autoimmunity·M D de SmetR B Nussenblatt
Mar 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aihua LiRakesh K Singh
Mar 23, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Felix MorIrun R Cohen
Apr 16, 2005·Neuro-oncology·Daniel J BratErwin G Van Meir
May 26, 2006·The British Journal of Ophthalmology·M S SpitzerUNKNOWN Tuebingen Bevacizumab Study Group
Aug 28, 2007·Cell·Sunyoung LeeM Luisa Iruela-Arispe
Jul 26, 2008·Progress in Retinal and Eye Research·J S PennM E Hartnett
Oct 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Magali Saint-GeniezPatricia A D'Amore
Dec 17, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aninda BasuDavid M Briscoe
Jun 22, 2010·Journal of Cellular Biochemistry·José Prisco Palma-NicolásAna María López-Colomé
Aug 13, 2010·Developments in Ophthalmology·Maurizio Battaglia ParodiFrancesco Bandello
Aug 26, 2010·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Arnd HeiligenhausGerhild Wildner
Dec 6, 2012·Investigative Ophthalmology & Visual Science·Martin BuschArnd Heiligenhaus
Dec 29, 2016·Progress in Retinal and Eye Research·Eva M Del AmoArto Urtti

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Citations

Sep 10, 2019·Expert Opinion on Emerging Drugs·Uwe PleyerJudith Rademacher
Oct 9, 2019·Seminars in Immunopathology·Gerhild Wildner, Maria Diedrichs-Möhring
Nov 3, 2020·Clinical & Translational Immunology·Denis Wakefield, Gerhild Wildner
Feb 27, 2021·International Ophthalmology·Uwe PleyerChristoph Deuter

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