Your browser doesn't support javascript.
loading
Neutrophils homing into the retina trigger pathology in early age-related macular degeneration.
Ghosh, Sayan; Padmanabhan, Archana; Vaidya, Tanuja; Watson, Alan M; Bhutto, Imran A; Hose, Stacey; Shang, Peng; Stepicheva, Nadezda; Yazdankhah, Meysam; Weiss, Joseph; Das, Manjula; Gopikrishna, Santosh; Yadav, Naresh; Berger, Thorsten; Mak, Tak W; Xia, Shuli; Qian, Jiang; Lutty, Gerard A; Jayagopal, Ashwath; Zigler, J Samuel; Sethu, Swaminathan; Handa, James T; Watkins, Simon C; Ghosh, Arkasubhra; Sinha, Debasish.
Afiliación
  • Ghosh S; 1Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA USA.
  • Padmanabhan A; 2Narayana Nethralaya Foundation, Bengaluru, India.
  • Vaidya T; 2Narayana Nethralaya Foundation, Bengaluru, India.
  • Watson AM; 3Center for Biologic Imaging and Department of Cellular Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA USA.
  • Bhutto IA; 1Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA USA.
  • Hose S; 1Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA USA.
  • Shang P; 1Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA USA.
  • Stepicheva N; 1Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA USA.
  • Yazdankhah M; 1Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA USA.
  • Weiss J; 1Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA USA.
  • Das M; Beyond Antibody, Bengaluru, India.
  • Gopikrishna S; 2Narayana Nethralaya Foundation, Bengaluru, India.
  • Aishwarya; 2Narayana Nethralaya Foundation, Bengaluru, India.
  • Yadav N; 2Narayana Nethralaya Foundation, Bengaluru, India.
  • Berger T; 5The Campbell Family Institute for Breast Cancer Research and Ontario Cancer Institute, University Health Network, Toronto, ON Canada.
  • Mak TW; 5The Campbell Family Institute for Breast Cancer Research and Ontario Cancer Institute, University Health Network, Toronto, ON Canada.
  • Xia S; 6Hugo W. Moser Research Institute at Kennedy Krieger, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD USA.
  • Qian J; 7The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD USA.
  • Lutty GA; 7The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD USA.
  • Jayagopal A; 8Pharma Research and Early Development, Roche Innovation Center, F. Hoffmann-La Roche, Ltd, Basel, Switzerland.
  • Zigler JS; Present Address: Kodiak Sciences, Palo Alto, CA USA.
  • Sethu S; 7The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD USA.
  • Handa JT; 2Narayana Nethralaya Foundation, Bengaluru, India.
  • Watkins SC; 7The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD USA.
  • Ghosh A; 3Center for Biologic Imaging and Department of Cellular Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA USA.
  • Sinha D; 2Narayana Nethralaya Foundation, Bengaluru, India.
Commun Biol ; 2: 348, 2019.
Article en En | MEDLINE | ID: mdl-31552301
Age-related macular degeneration (AMD) is an expanding problem as longevity increases worldwide. While inflammation clearly contributes to vision loss in AMD, the mechanism remains controversial. Here we show that neutrophils are important in this inflammatory process. In the retinas of both early AMD patients and in a mouse model with an early AMD-like phenotype, we show neutrophil infiltration. Such infiltration was confirmed experimentally using ribbon-scanning confocal microscopy (RSCM) and IFNλ- activated dye labeled normal neutrophils. With neutrophils lacking lipocalin-2 (LCN-2), infiltration was greatly reduced. Further, increased levels of IFNλ in early AMD trigger neutrophil activation and LCN-2 upregulation. LCN-2 promotes inflammation by modulating integrin ß1 levels to stimulate adhesion and transmigration of activated neutrophils into the retina. We show that in the mouse model, inhibiting AKT2 neutralizes IFNλ inflammatory signals, reduces LCN-2-mediated neutrophil infiltration, and reverses early AMD-like phenotype changes. Thus, AKT2 inhibitors may have therapeutic potential in early, dry AMD.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Retina / Degeneración Macular / Neutrófilos Límite: Aged / Aged80 / Animals / Female / Humans / Male Idioma: En Revista: Commun Biol Año: 2019 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Retina / Degeneración Macular / Neutrófilos Límite: Aged / Aged80 / Animals / Female / Humans / Male Idioma: En Revista: Commun Biol Año: 2019 Tipo del documento: Article Pais de publicación: Reino Unido