PMID- 28903153
OWN - NLM
STAT- MEDLINE
DCOM- 20170922
LR  - 20181113
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 58
IP  - 11
DP  - 2017 Sep 1
TI  - Colony Stimulating Factor-1 Receptor Expressing Cells Infiltrating the Cornea
      Control Corneal Nerve Degeneration in Response to HSV-1 Infection.
PG  - 4670-4682
LID - 10.1167/iovs.17-22159 [doi]
AB  - Purpose: Herpes simplex virus type-1 (HSV-1) is a leading cause of neurotrophic
      keratitis, characterized by decreased or absent corneal sensation due to damage
      to the sensory corneal innervation. We previously reported the elicited immune
      response to infection contributes to the mechanism of corneal nerve
      regression/damage during acute HSV-1 infection. Our aim is to further establish
      the involvement of infiltrated macrophages in the mechanism of nerve loss upon
      infection. Methods: Macrophage Fas-Induced Apoptosis (MAFIA) transgenic C57BL/6
      mice were systemically treated with AP20187 dimerizer or vehicle (VEH), and their
      corneas, lymph nodes, and blood were assessed for CD45+CD11b+GFP+ cell depletion 
      by flow cytometry (FC). Mice were ocularly infected with HSV-1 or left
      uninfected. At 2, 4, and/or 6 days post infection (PI), corneas were assessed for
      sensitivity and harvested for FC, nerve structure by immunohistochemistry, viral 
      content by plaque assay, soluble factor content by suspension array, and
      activation of signaling pathways by Western blot analysis. C57BL6 mice were used 
      to compare to the MAFIA mouse model. Results: MAFIA mice treated with AP20187 had
      efficient depletion of CD45+CD11b+GFP+ cells in the tissues analyzed. The
      reduction of CD45+CD11b+GFP+ cells recruited to the infected corneas of
      AP20187-treated mice correlated with preservation of corneal nerve structure and 
      function, decreased protein concentration of inflammatory cytokines, and
      decreased STAT3 activation despite no changes in viral content in the cornea
      compared to VEH-treated animals. Conclusions: Our results suggest infiltrated
      macrophages are early effectors in the nerve regression following HSV-1
      infection. We propose the neurodegeneration mechanism involves macrophages, local
      up-regulation of IL-6, and activation of STAT3.
FAU - Chucair-Elliott, Ana J
AU  - Chucair-Elliott AJ
AD  - Department of Ophthalmology, University of Oklahoma Health Sciences Center,
      Oklahoma City, Oklahoma, United States.
FAU - Gurung, Hem R
AU  - Gurung HR
AD  - Microbiology and Immunology, University of Oklahoma Health Sciences Center,
      Oklahoma City, Oklahoma, United States.
FAU - Carr, Meghan M
AU  - Carr MM
AD  - Department of Ophthalmology, University of Oklahoma Health Sciences Center,
      Oklahoma City, Oklahoma, United States.
FAU - Carr, Daniel J J
AU  - Carr DJJ
AD  - Department of Ophthalmology, University of Oklahoma Health Sciences Center,
      Oklahoma City, Oklahoma, United States.
AD  - Microbiology and Immunology, University of Oklahoma Health Sciences Center,
      Oklahoma City, Oklahoma, United States.
LA  - eng
GR  - P30 EY021725/EY/NEI NIH HHS/United States
GR  - R01 EY021238/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (AP20187)
RN  - 0 (Interleukin-6)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (interleukin-6, mouse)
RN  - EC 2.7.10.1 (Receptor, Macrophage Colony-Stimulating Factor)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cornea/*innervation
MH  - Disease Models, Animal
MH  - Flow Cytometry
MH  - Herpesvirus 1, Human/*growth & development
MH  - Immunohistochemistry
MH  - Interleukin-6/metabolism
MH  - Keratitis, Herpetic/*immunology/pathology/virology
MH  - Macrophages/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Nerve Degeneration/*immunology/pathology/virology
MH  - Receptor, Macrophage Colony-Stimulating Factor/*metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Tacrolimus/analogs & derivatives/pharmacology
MH  - Trigeminal Nerve/metabolism
MH  - Trigeminal Nerve Diseases/*immunology/pathology/virology
MH  - Viral Plaque Assay
PMC - PMC5597033
EDAT- 2017/09/14 06:00
MHDA- 2017/09/25 06:00
CRDT- 2017/09/14 06:00
PHST- 2017/09/14 06:00 [entrez]
PHST- 2017/09/14 06:00 [pubmed]
PHST- 2017/09/25 06:00 [medline]
AID - 2654117 [pii]
AID - 10.1167/iovs.17-22159 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2017 Sep 1;58(11):4670-4682. doi:
      10.1167/iovs.17-22159.