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- Publisher Website: 10.1038/s42003-019-0588-y
- Scopus: eid_2-s2.0-85073241770
- PMID: 31552301
- WOS: WOS:000488308200001
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Article: Neutrophils homing into the retina trigger pathology in early age-related macular degeneration
Title | Neutrophils homing into the retina trigger pathology in early age-related macular degeneration |
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Authors | Ghosh, SayanPadmanabhan, ArchanaVaidya, TanujaWatson, Alan M.Bhutto, Imran A.Hose, StaceyShang, PengStepicheva, NadezdaYazdankhah, MeysamWeiss, JosephDas, ManjulaGopikrishna, SantoshAishwaryaYadav, NareshBerger, ThorstenMak, Tak W.Xia, ShuliQian, JiangLutty, Gerard A.Jayagopal, AshwathZigler, J. SamuelSethu, SwaminathanHanda, James T.Watkins, Simon C.Ghosh, ArkasubhraSinha, Debasish |
Issue Date | 2019 |
Citation | Communications Biology, 2019, v. 2, n. 1, article no. 348 How to Cite? |
Abstract | 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 β1 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. |
Persistent Identifier | http://hdl.handle.net/10722/292127 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Ghosh, Sayan | - |
dc.contributor.author | Padmanabhan, Archana | - |
dc.contributor.author | Vaidya, Tanuja | - |
dc.contributor.author | Watson, Alan M. | - |
dc.contributor.author | Bhutto, Imran A. | - |
dc.contributor.author | Hose, Stacey | - |
dc.contributor.author | Shang, Peng | - |
dc.contributor.author | Stepicheva, Nadezda | - |
dc.contributor.author | Yazdankhah, Meysam | - |
dc.contributor.author | Weiss, Joseph | - |
dc.contributor.author | Das, Manjula | - |
dc.contributor.author | Gopikrishna, Santosh | - |
dc.contributor.author | Aishwarya | - |
dc.contributor.author | Yadav, Naresh | - |
dc.contributor.author | Berger, Thorsten | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Xia, Shuli | - |
dc.contributor.author | Qian, Jiang | - |
dc.contributor.author | Lutty, Gerard A. | - |
dc.contributor.author | Jayagopal, Ashwath | - |
dc.contributor.author | Zigler, J. Samuel | - |
dc.contributor.author | Sethu, Swaminathan | - |
dc.contributor.author | Handa, James T. | - |
dc.contributor.author | Watkins, Simon C. | - |
dc.contributor.author | Ghosh, Arkasubhra | - |
dc.contributor.author | Sinha, Debasish | - |
dc.date.accessioned | 2020-11-17T14:55:49Z | - |
dc.date.available | 2020-11-17T14:55:49Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Communications Biology, 2019, v. 2, n. 1, article no. 348 | - |
dc.identifier.uri | http://hdl.handle.net/10722/292127 | - |
dc.description.abstract | 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 β1 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. | - |
dc.language | eng | - |
dc.relation.ispartof | Communications Biology | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | Neutrophils homing into the retina trigger pathology in early age-related macular degeneration | - |
dc.type | Article | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1038/s42003-019-0588-y | - |
dc.identifier.pmid | 31552301 | - |
dc.identifier.pmcid | PMC6754381 | - |
dc.identifier.scopus | eid_2-s2.0-85073241770 | - |
dc.identifier.volume | 2 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | article no. 348 | - |
dc.identifier.epage | article no. 348 | - |
dc.identifier.eissn | 2399-3642 | - |
dc.identifier.isi | WOS:000488308200001 | - |
dc.identifier.issnl | 2399-3642 | - |