Universität zu Köln

Madeira, M. H., Rashid, K., Ambrosio, A. F., Santiago, A. R. and Langmann, T. (2018). Blockade of microglial adenosine A2A receptor impacts inflammatory mechanisms, reduces ARPE-19 cell dysfunction and prevents photoreceptor loss in vitro. Sci Rep, 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Age-related macular degeneration (AMD) is characterized by pathological changes in the retinal pigment epithelium (RPE) and loss of photoreceptors. Growing evidence has demonstrated that reactive microglial cells trigger RPE dysfunction and loss of photoreceptors, and inflammasome pathways and complement activation contribute to AMD pathogenesis. We and others have previously shown that adenosine A(2A) receptor (A(2A)R) blockade prevents microglia-mediated neuroinflammatory processes and mediates protection to the retina. However, it is still unknown whether blocking A(2A)R in microglia protects against the pathological features of AMD. Herein, we show that an A(2A)R antagonist, SCH58261, prevents the upregulation of the expression of pro-inflammatory mediators and the alterations in the complement system triggered by an inflammatory challenge in human microglial cells. Furthermore, blockade of A(2A)R in microglia decreases the inflammatory response, as well as complement and inflammasome activation, in ARPE-19 cells exposed to conditioned medium of activated microglia. Finally, we also show that blocking A(2A)R in human microglia increases the clearance of apoptotic photoreceptors. This study opens the possibility of using selective A(2A)R antagonists in therapy for AMD, by modulating the interplay between microglia, RPE and photoreceptors.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Madeira, M. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rashid, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ambrosio, A. F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Santiago, A. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Langmann, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-196264
DOI:	10.1038/s41598-018-20733-2
Journal or Publication Title:	Sci Rep
Volume:	8
Date:	2018
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RETINAL-PIGMENT EPITHELIUM; COMPLEMENT ACTIVATION; MACULAR DEGENERATION; NLRP3 INFLAMMASOME; LYSOSOMAL DESTABILIZATION; GANGLION-CELLS; AUTOPHAGY; DEATH; NEUROINFLAMMATION; SUSCEPTIBILITY Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19626