PMID- 30665231
OWN - NLM
STAT- In-Data-Review
LR  - 20190127
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 60
IP  - 1
DP  - 2019 Jan 2
TI  - Optic Nerve Head Astrocytes Display Axon-Dependent and -Independent Reactivity in
      Response to Acutely Elevated Intraocular Pressure.
PG  - 312-321
LID - 10.1167/iovs.18-25447 [doi]
AB  - Purpose: Optic nerve head (ONH) astrocytes provide support for axons, but exhibit
      structural and functional changes (termed reactivity) in a number of glaucoma
      models. The purpose of this study was to determine if ONH astrocyte structural
      reactivity is axon-dependent. Methods: Using rats, we combine retrobulbar optic
      nerve transection (ONT) with acute controlled elevation of intraocular pressure
      (CEI), to induce total optic nerve axon loss and ONH astrocyte reactivity,
      respectively. Animals were euthanized immediately or 1 day post CEI, in the
      presence or absence of ONT. ONH sections were labeled with fluorescent-tagged
      phalloidin and antibodies against beta3 tubulin, phosphorylated cortactin,
      phosphorylated paxillin, or complement C3. ONH label intensities were quantified 
      after confocal microscopy. Retrobulbar nerves were assessed for axon injury by
      light microscopy. Results: While ONT alone had no effect on ONH astrocyte
      structural orientation, astrocytes demonstrated significant reorganization of
      cellular extensions within hours after CEI, even when combined with ONT. However,
      ONH astrocytes displayed differential intensities of actin (phosphorylated
      cortactin) and focal adhesion (phosphorylated paxillin) mediators in response to 
      CEI alone, ONT alone, or the combination of CEI and ONT. Lastly, label
      intensities of complement C3 within the ONH were unchanged in eyes subjected to
      CEI alone, ONT alone, or the combination of CEI and ONT, relative to controls.
      Conclusions: Early ONH astrocyte structural reactivity to elevated IOP is
      multifaceted, displaying both axon dependent and independent responses. These
      findings have important implications for pursuing astrocytes as diagnostic and
      therapeutic targets in neurodegenerative disorders with fluctuating levels of
      axon injury.
FAU - Tehrani, Shandiz
AU  - Tehrani S
AD  - Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science
      University, Portland, Oregon, United States.
FAU - Davis, Lauren
AU  - Davis L
AD  - Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science
      University, Portland, Oregon, United States.
FAU - Cepurna, William O
AU  - Cepurna WO
AD  - Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science
      University, Portland, Oregon, United States.
FAU - Delf, R Katherine
AU  - Delf RK
AD  - Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science
      University, Portland, Oregon, United States.
FAU - Lozano, Diana C
AU  - Lozano DC
AD  - Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science
      University, Portland, Oregon, United States.
FAU - Choe, Tiffany E
AU  - Choe TE
AD  - Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science
      University, Portland, Oregon, United States.
FAU - Johnson, Elaine C
AU  - Johnson EC
AD  - Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science
      University, Portland, Oregon, United States.
FAU - Morrison, John C
AU  - Morrison JC
AD  - Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science
      University, Portland, Oregon, United States.
LA  - eng
GR  - K08 EY024025/EY/NEI NIH HHS/United States
GR  - P30 EY010572/EY/NEI NIH HHS/United States
GR  - R01 EY010145/EY/NEI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
PMC - PMC6343680
EDAT- 2019/01/22 06:00
MHDA- 2019/01/22 06:00
CRDT- 2019/01/22 06:00
PHST- 2019/01/22 06:00 [entrez]
PHST- 2019/01/22 06:00 [pubmed]
PHST- 2019/01/22 06:00 [medline]
AID - 2722995 [pii]
AID - 10.1167/iovs.18-25447 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2019 Jan 2;60(1):312-321. doi: 10.1167/iovs.18-25447.