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First Responders: Dynamics of Pre-Gliotic Müller Cell Responses in The Isolated Adult Rat Retina.

Taylor, Linnéa LU ; Arnér, Karin LU and Ghosh, Fredrik LU (2015) In Current Eye Research 40(12). p.1245-1260
Abstract
Abstract Purpose: To explore the early reactions of the retinal Müller glia in response to retinal insult prior to gliotic remodeling and the sustained upregulation of intermediate filament glial fibrillary acidic protein (GFAP), which has traditionally been considered the most sensitive early indicator of reactive gliosis. Methods: To study pre-gliotic events, we used a model of adult rat retinal explants and related the dynamic expression of GFAP as well as apoptosis, to four key regulators of retinal homeostasis (glutamine synthetase (GS), cellular retinaldehyde binding protein (CRALBP), basic fibroblast growth factor (bFGF), carbonic anhydrase II (CAII)) using immunohistochemistry. Results: We found that a sustained GFAP upregulation... (More)
Abstract Purpose: To explore the early reactions of the retinal Müller glia in response to retinal insult prior to gliotic remodeling and the sustained upregulation of intermediate filament glial fibrillary acidic protein (GFAP), which has traditionally been considered the most sensitive early indicator of reactive gliosis. Methods: To study pre-gliotic events, we used a model of adult rat retinal explants and related the dynamic expression of GFAP as well as apoptosis, to four key regulators of retinal homeostasis (glutamine synthetase (GS), cellular retinaldehyde binding protein (CRALBP), basic fibroblast growth factor (bFGF), carbonic anhydrase II (CAII)) using immunohistochemistry. Results: We found that a sustained GFAP upregulation couple with gliotic remodeling occurred comparatively late and that this phenomenon was preceded by an initial upregulation followed by depletion of GS, CRALBP, bFGF and CAII in retinal Müller cells. The initial increase of the regulatory proteins, seen after 1-12 h, preceded a first phase of moderate apoptosis, and their depletion after 48 h was followed by massive apoptosis and widespread GFAP upregulation in the Müller cells at 5 days. Conclusion: We conclude that, in the explant model, changes in the expression of the four homeostatic regulatory proteins as well as apoptotic cell death precedes sustained GFAP upregulation and reactive gliosis. Müller cell reactivity has been linked to several retinal conditions, and the herein provided novel information on the dynamics of pre-gliotic events in the lesioned retina may help us understand important pathological mechanisms crucial for future therapeutic intervention. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Current Eye Research
volume
40
issue
12
pages
1245 - 1260
publisher
Taylor & Francis
external identifiers
  • pmid:25495492
  • scopus:84959338647
  • wos:000369891900008
ISSN
0271-3683
DOI
10.3109/02713683.2014.988360
language
English
LU publication?
yes
id
3b82ec8c-5727-4e70-9d7f-c2b243d7713e (old id 4908587)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25495492?dopt=Abstract
date added to LUP
2015-01-10 18:09:25
date last changed
2017-10-22 04:51:00
@article{3b82ec8c-5727-4e70-9d7f-c2b243d7713e,
  abstract     = {Abstract Purpose: To explore the early reactions of the retinal Müller glia in response to retinal insult prior to gliotic remodeling and the sustained upregulation of intermediate filament glial fibrillary acidic protein (GFAP), which has traditionally been considered the most sensitive early indicator of reactive gliosis. Methods: To study pre-gliotic events, we used a model of adult rat retinal explants and related the dynamic expression of GFAP as well as apoptosis, to four key regulators of retinal homeostasis (glutamine synthetase (GS), cellular retinaldehyde binding protein (CRALBP), basic fibroblast growth factor (bFGF), carbonic anhydrase II (CAII)) using immunohistochemistry. Results: We found that a sustained GFAP upregulation couple with gliotic remodeling occurred comparatively late and that this phenomenon was preceded by an initial upregulation followed by depletion of GS, CRALBP, bFGF and CAII in retinal Müller cells. The initial increase of the regulatory proteins, seen after 1-12 h, preceded a first phase of moderate apoptosis, and their depletion after 48 h was followed by massive apoptosis and widespread GFAP upregulation in the Müller cells at 5 days. Conclusion: We conclude that, in the explant model, changes in the expression of the four homeostatic regulatory proteins as well as apoptotic cell death precedes sustained GFAP upregulation and reactive gliosis. Müller cell reactivity has been linked to several retinal conditions, and the herein provided novel information on the dynamics of pre-gliotic events in the lesioned retina may help us understand important pathological mechanisms crucial for future therapeutic intervention.},
  author       = {Taylor, Linnéa and Arnér, Karin and Ghosh, Fredrik},
  issn         = {0271-3683},
  language     = {eng},
  number       = {12},
  pages        = {1245--1260},
  publisher    = {Taylor & Francis},
  series       = {Current Eye Research},
  title        = {First Responders: Dynamics of Pre-Gliotic Müller Cell Responses in The Isolated Adult Rat Retina.},
  url          = {http://dx.doi.org/10.3109/02713683.2014.988360},
  volume       = {40},
  year         = {2015},
}