{"entity": "publication", "iuid": "f4fcab808cfd40e783fd312016f391a9", "timestamp": "2026-08-29T04:22:58.506Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f4fcab808cfd40e783fd312016f391a9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f4fcab808cfd40e783fd312016f391a9"}}, "title": "Caspase-8 modulates physiological and pathological angiogenesis during retina development.", "authors": [{"family": "Tisch", "given": "Nathalie", "initials": "N"}, {"family": "Freire-Valls", "given": "Aida", "initials": "A"}, {"family": "Yerbes", "given": "Rosario", "initials": "R"}, {"family": "Paredes", "given": "Isidora", "initials": "I"}, {"family": "La Porta", "given": "Silvia", "initials": "S"}, {"family": "Wang", "given": "Xiaohong", "initials": "X"}, {"family": "Mart\u00edn-P\u00e9rez", "given": "Rosa", "initials": "R"}, {"family": "Castro", "given": "Laura", "initials": "L"}, {"family": "Wong", "given": "Wendy Wei-Lynn", "initials": "WW"}, {"family": "Coultas", "given": "Leigh", "initials": "L"}, {"family": "Strilic", "given": "Boris", "initials": "B"}, {"family": "Gr\u00f6ne", "given": "Hermann-Josef", "initials": "HJ"}, {"family": "Hielscher", "given": "Thomas", "initials": "T"}, {"family": "Mogler", "given": "Carolin", "initials": "C"}, {"family": "Adams", "given": "Ralf H", "initials": "RH"}, {"family": "Heiduschka", "given": "Peter", "initials": "P"}, {"family": "Claesson-Welsh", "given": "Lena", "initials": "L"}, {"family": "Mazzone", "given": "Massimiliano", "initials": "M"}, {"family": "L\u00f3pez-Rivas", "given": "Abelardo", "initials": "A"}, {"family": "Schmidt", "given": "Thomas", "initials": "T"}, {"family": "Augustin", "given": "Hellmut G", "initials": "HG"}, {"family": "Ruiz de Almodovar", "given": "Carmen", "initials": "C"}], "type": "journal article", "published": "2019-12-02", "journal": {"title": "J. Clin. Invest.", "issn": "1558-8238", "volume": "129", "issue": "12", "pages": "5092-5107", "issn-l": "0021-9738"}, "abstract": "During developmental angiogenesis, blood vessels grow and remodel to ultimately build a hierarchical vascular network. Whether, how, cell death signaling molecules contribute to blood vessel formation is still not well understood. Caspase-8 (Casp-8), a key protease in the extrinsic cell death-signaling pathway, regulates cell death via both apoptosis and necroptosis. Here, we show that expression of Casp-8 in endothelial cells (ECs) is required for proper postnatal retina angiogenesis. EC-specific Casp-8-KO pups (Casp-8ECKO) showed reduced retina angiogenesis, as the loss of Casp-8 reduced EC proliferation, sprouting, and migration independently of its cell death function. Instead, the loss of Casp-8 caused hyperactivation of p38 MAPK downstream of receptor-interacting serine/threonine protein kinase 3 (RIPK3) and destabilization of vascular endothelial cadherin (VE-cadherin) at EC junctions. In a mouse model of oxygen-induced retinopathy (OIR) resembling retinopathy of prematurity (ROP), loss of Casp-8 in ECs was beneficial, as pathological neovascularization was reduced in Casp-8ECKO pups. Taking these data together, we show that Casp-8 acts in a cell death-independent manner in ECs to regulate the formation of the retina vasculature and that Casp-8 in ECs is mechanistically involved in the pathophysiology of ROP.", "doi": "10.1172/JCI122767", "pmid": "31454332", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6877326"}, {"db": "pii", "key": "122767"}], "notes": [], "created": "2026-08-21T12:31:38.250Z", "modified": "2026-08-21T12:31:38.289Z"}