Open AccessActivated monocytes resist elimination by retinal pigment epithelium and downregulate their OTX 2 expression via TNF ‐α
Author(s) -
Mathis Thibaud,
Housset Michael,
Eandi Chiara,
Beguier Fanny,
Touhami Sara,
Reichman Sacha,
Augustin Sebastien,
Gondouin Pauline,
Sahel JoséAlain,
Kodjikian Laurent,
Goureau Olivier,
Guillonneau Xavier,
Sennlaub Florian
Publication year - 2017
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12540
Subject(s) - downregulation and upregulation , biology , microbiology and biotechnology , retinal pigment epithelium , cd14 , retinal , visual phototransduction , macular degeneration , inflammation , retina , induced pluripotent stem cell , tumor necrosis factor alpha , eye development , immunology , neuroscience , immune system , gene , medicine , transcription factor , biochemistry , embryonic stem cell , ophthalmology
Summary Orthodenticle homeobox 2 ( OTX 2) controls essential, homeostatic retinal pigment epithelial ( RPE ) genes in the adult. Using cocultures of human CD 14 + blood monocytes (Mos) and primary porcine RPE cells and a fully humanized system using human‐induced pluripotent stem cell‐derived RPE cells, we show that activated Mos markedly inhibit RPE OTX 2 expression and resist elimination in contact with the immunosuppressive RPE . Mechanistically, we demonstrate that TNF ‐α, secreted from activated Mos, mediates the downregulation of OTX 2 and essential RPE genes of the visual cycle among others. Our data show how subretinal, chronic inflammation and in particular TNF ‐α can affect RPE function, which might contribute to the visual dysfunctions in diseases such as age‐related macular degeneration ( AMD ) where subretinal macrophages are observed. Our findings provide important mechanistic insights into the regulation of OTX 2 under inflammatory conditions. Therapeutic restoration of OTX 2 expression might help revive RPE and visual function in retinal diseases such as AMD .