PMID- 32645232
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20211214
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Linking)
VI  - 68
IP  - 12
DP  - 2020 Dec
TI  - Tightening the retinal glia limitans attenuates neuroinflammation after optic 
      nerve injury.
PG  - 2643-2660
LID - 10.1002/glia.23875 [doi]
AB  - Increasing evidence suggests that functional impairments at the level of the 
      neurovascular unit (NVU) underlie many neurodegenerative and neuroinflammatory 
      diseases. While being part of the NVU, astrocytes have been largely overlooked in 
      this context and only recently, tightening of the glia limitans has been put 
      forward as an important neuroprotective response to limit these injurious 
      processes. In this study, using the retina as a central nervous system (CNS) 
      model organ, we investigated the structure and function of the glia limitans, and 
      reveal that the blood-retina barrier and glia limitans function as a coordinated 
      double barrier to limit infiltration of leukocytes and immune molecules. We 
      provide in vitro and in vivo evidence for a protective response at the NVU upon 
      CNS injury, which evokes inflammation-induced glia limitans tightening. Matrix 
      metalloproteinase-3 (MMP-3) was found to be a crucial regulator of this process, 
      thereby revealing its beneficial and immunomodulatory role in the CNS. in vivo 
      experiments in which MMP-3 activity was deleted via genetic and pharmacological 
      approaches, combined with a comprehensive study of tight junction molecules, 
      glial end feet markers, myeloid cell infiltration, cytokine expression and 
      neurodegeneration, show that MMP-3 attenuates neuroinflammation and 
      neurodegeneration by tightening the glia limitans, thereby pointing to a 
      prominent role of MMP-3 in preserving the integrity of the NVU upon injury. 
      Finally, we gathered promising evidence to suggest that IL1b, which is also 
      regulated by MMP-3, is at least one of the molecular messengers that induces glia 
      limitans tightening in the injured CNS.
CI  - (c) 2020 Wiley Periodicals LLC.
FAU - Lefevere, Evy
AU  - Lefevere E
AD  - Neural Circuit Development and Regeneration Research Group, Department of 
      Biology, KU Leuven, Leuven, Belgium.
AD  - Leuven Brain Institute (LBI), KU Leuven, Leuven, Belgium.
FAU - Salinas-Navarro, Manuel
AU  - Salinas-Navarro M
AD  - Neural Circuit Development and Regeneration Research Group, Department of 
      Biology, KU Leuven, Leuven, Belgium.
AD  - Leuven Brain Institute (LBI), KU Leuven, Leuven, Belgium.
FAU - Andries, Lien
AU  - Andries L
AD  - Neural Circuit Development and Regeneration Research Group, Department of 
      Biology, KU Leuven, Leuven, Belgium.
AD  - Leuven Brain Institute (LBI), KU Leuven, Leuven, Belgium.
FAU - Noterdaeme, Lut
AU  - Noterdaeme L
AD  - Neural Circuit Development and Regeneration Research Group, Department of 
      Biology, KU Leuven, Leuven, Belgium.
FAU - Etienne, Isabelle
AU  - Etienne I
AD  - Oxurion NV, Leuven, Belgium.
FAU - Van Wonterghem, Elien
AU  - Van Wonterghem E
AD  - Barriers in Inflammation Lab, VIB Center for Inflammation Research, Ghent, 
      Belgium.
AD  - Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
FAU - Vinckier, Stefan
AU  - Vinckier S
AD  - Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, 
      and Department of Oncology and Leuven Cancer Institute (LKI), VIB and KU Leuven, 
      Leuven, Belgium.
FAU - Davis, Benjamin M
AU  - Davis BM
AD  - Glaucoma and Retinal Neurodegeneration Research, Visual Neuroscience, UCL 
      Institute of Ophthalmology, London, UK.
FAU - Van Bergen, Tine
AU  - Van Bergen T
AD  - Oxurion NV, Leuven, Belgium.
FAU - Van Hove, Inge
AU  - Van Hove I
AD  - Neural Circuit Development and Regeneration Research Group, Department of 
      Biology, KU Leuven, Leuven, Belgium.
AD  - Oxurion NV, Leuven, Belgium.
FAU - Movahedi, Kiavash
AU  - Movahedi K
AD  - Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, 
      Belgium.
AD  - Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, 
      Belgium.
FAU - Vandenbroucke, Roosmarijn E
AU  - Vandenbroucke RE
AD  - Barriers in Inflammation Lab, VIB Center for Inflammation Research, Ghent, 
      Belgium.
AD  - Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
FAU - Moons, Lieve
AU  - Moons L
AUID- ORCID: 0000-0003-0186-1411
AD  - Neural Circuit Development and Regeneration Research Group, Department of 
      Biology, KU Leuven, Leuven, Belgium.
AD  - Leuven Brain Institute (LBI), KU Leuven, Leuven, Belgium.
FAU - De Groef, Lies
AU  - De Groef L
AUID- ORCID: 0000-0002-3329-3474
AD  - Neural Circuit Development and Regeneration Research Group, Department of 
      Biology, KU Leuven, Leuven, Belgium.
AD  - Leuven Brain Institute (LBI), KU Leuven, Leuven, Belgium.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200709
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Astrocytes
MH  - Humans
MH  - Matrix Metalloproteinase 3
MH  - Neuroglia
MH  - *Optic Nerve Injuries
MH  - Retina
OTO - NOTNLM
OT  - glia limitans
OT  - matrix metalloproteinase-3
OT  - neurodegeneration
OT  - neuroinflammation
OT  - optic nerve crush
EDAT- 2020/07/10 06:00
MHDA- 2021/12/15 06:00
CRDT- 2020/07/10 06:00
PHST- 2020/01/20 00:00 [received]
PHST- 2020/05/20 00:00 [revised]
PHST- 2020/06/04 00:00 [accepted]
PHST- 2020/07/10 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2020/07/10 06:00 [entrez]
AID - 10.1002/glia.23875 [doi]
PST - ppublish
SO  - Glia. 2020 Dec;68(12):2643-2660. doi: 10.1002/glia.23875. Epub 2020 Jul 9.