PMID- 30332778
OWN - NLM
STAT- MEDLINE
DCOM- 20190121
LR  - 20190121
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 10
DP  - 2018 Oct 16
TI  - Thrombospondin-1 Is Necessary for the Development and Repair of Corneal Nerves.
LID - 10.3390/ijms19103191 [doi]
LID - 3191
AB  - Thrombospondin-1-deficient (TSP-1(-/-)) mice are used as an animal model of 
      Sjogren's Syndrome because they exhibit many of the symptoms associated with the 
      autoimmune type of dry eye found in primary Sjogren's Syndrome. This type of dry 
      eye is linked to the inflammation of the lacrimal gland, conjunctiva, and cornea, 
      and is thought to involve dysfunction of the complex neuronal reflex arc that 
      mediates tear production in response to noxious stimuli on the ocular surface. 
      This study characterizes the structural and functional changes to the corneal 
      nerves that are the afferent arm of this arc in young and older TSP-1(-/-) and 
      wild type (WT) mice. The structure and subtype of nerves were characterized by 
      immunohistochemistry, in vivo confocal microscopy, and confocal microscopy. 
      Cytokine expression analysis was determined by Q-PCR and the number of monocytes 
      was measured by immunohistochemistry. We found that only the pro-inflammatory 
      cytokine MIP-2 increased in young corneas of TSP-1(-/-) compared to WT mice, but 
      tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), and 
      macrophage inflammatory protein-2 (MIP-2) all increased in older TSP-1(-/-) mouse 
      corneas. In contrast, CD11b+ pro-inflammatory monocytes did not increase even in 
      older mouse corneas. Calcitonin gene-related peptide (CGRP)-, but not Substance P 
      (SubP)-containing corneal nerves decreased in older, but not younger TSP-1(-/-) 
      compared to WT mouse corneas. We conclude that CGRP-containing corneal sensory 
      nerves exhibit distinct structural deficiencies as disease progresses in 
      TSP-1(-/-) mice, suggesting that: (1) TSP-1 is needed for the development or 
      repair of these nerves and (2) impaired afferent corneal nerve structure and 
      hence function may contribute to ocular surface dysfunction that develops as 
      TSP-1(-/-) mice age.
FAU - Tatematsu, Yukako
AU  - Tatematsu Y
AD  - Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of 
      Ophthalmology, Harvard Medical School, Boston, MA 02114, USA. 
      yuka.tatematsu@gmail.com.
FAU - Khan, Qalbi
AU  - Khan Q
AD  - Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of 
      Ophthalmology, Harvard Medical School, Boston, MA 02114, USA. Qalbi.khan@uit.no.
AD  - Department of Medical Biology, Faculty of Health Sciences, University of Tromso, 
      Tromso 9037, Norway. Qalbi.khan@uit.no.
FAU - Blanco, Tomas
AU  - Blanco T
AD  - Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of 
      Ophthalmology, Harvard Medical School, Boston, MA 02114, USA. 
      tomas_blanco@meei.harvard.edu.
FAU - Bair, Jeffrey A
AU  - Bair JA
AD  - Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of 
      Ophthalmology, Harvard Medical School, Boston, MA 02114, USA. 
      Jeffrey_Bair@meei.harvard.edu.
FAU - Hodges, Robin R
AU  - Hodges RR
AD  - Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of 
      Ophthalmology, Harvard Medical School, Boston, MA 02114, USA. 
      robin_hodges@meei.harvard.edu.
FAU - Masli, Sharmila
AU  - Masli S
AD  - Department of Ophthalmology, Boston University School of Medicine, Boston, MA 
      02118, USA. smasli@bu.edu.
FAU - Dartt, Darlene A
AU  - Dartt DA
AD  - Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of 
      Ophthalmology, Harvard Medical School, Boston, MA 02114, USA. 
      darlene_dartt@meei.harvard.edu.
LA  - eng
GR  - EY6177/GF/NIH HHS/United States
PT  - Journal Article
DEP - 20181016
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL2)
RN  - 0 (Cxcl2 protein, mouse)
RN  - 0 (Thrombospondin 1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 33507-63-0 (Substance P)
RN  - JHB2QIZ69Z (Calcitonin Gene-Related Peptide)
SB  - IM
MH  - Animals
MH  - Calcitonin Gene-Related Peptide/metabolism
MH  - Cell Count
MH  - Chemokine CCL2/metabolism
MH  - Chemokine CXCL2/metabolism
MH  - Cornea/*innervation/metabolism/*pathology
MH  - Corneal Stroma/pathology
MH  - Epithelium, Corneal/pathology
MH  - Mice
MH  - Monocytes/metabolism
MH  - *Nerve Regeneration
MH  - Staining and Labeling
MH  - Substance P/metabolism
MH  - Thrombospondin 1/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC6214039
OTO - NOTNLM
OT  - CGRP
OT  - Substance P
OT  - cornea
OT  - dry eye
OT  - sensory nerves
OT  - thrombospondin-1
COIS- The authors have no conflict of interest.
EDAT- 2018/10/20 06:00
MHDA- 2019/01/22 06:00
PMCR- 2018/10/01
CRDT- 2018/10/19 06:00
PHST- 2018/08/31 00:00 [received]
PHST- 2018/10/09 00:00 [revised]
PHST- 2018/10/10 00:00 [accepted]
PHST- 2018/10/19 06:00 [entrez]
PHST- 2018/10/20 06:00 [pubmed]
PHST- 2019/01/22 06:00 [medline]
PHST- 2018/10/01 00:00 [pmc-release]
AID - ijms19103191 [pii]
AID - ijms-19-03191 [pii]
AID - 10.3390/ijms19103191 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 Oct 16;19(10):3191. doi: 10.3390/ijms19103191.