PMID- 25495492 OWN - NLM STAT- MEDLINE DCOM- 20160706 LR - 20151104 IS - 1460-2202 (Electronic) IS - 0271-3683 (Linking) VI - 40 IP - 12 DP - 2015 TI - First responders: dynamics of pre-gliotic Muller cell responses in the isolated adult rat retina. PG - 1245-60 LID - 10.3109/02713683.2014.988360 [doi] AB - PURPOSE: To explore the early reactions of the retinal Muller 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 Muller 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 Muller 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. Muller 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. FAU - Taylor, Linnea AU - Taylor L AD - a Department of Ophthalmology , Lund University Hospital , Lund , Sweden. FAU - Arner, Karin AU - Arner K AD - a Department of Ophthalmology , Lund University Hospital , Lund , Sweden. FAU - Ghosh, Fredrik AU - Ghosh F AD - a Department of Ophthalmology , Lund University Hospital , Lund , Sweden. LA - eng PT - Journal Article DEP - 20141211 PL - England TA - Curr Eye Res JT - Current eye research JID - 8104312 RN - 0 (11-cis-retinal-binding protein) RN - 0 (Carrier Proteins) RN - 0 (Glial Fibrillary Acidic Protein) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - EC 4.2.1.- (Carbonic Anhydrase II) RN - EC 6.3.1.2 (Glutamate-Ammonia Ligase) SB - IM MH - Animals MH - Apoptosis MH - Carbonic Anhydrase II/*metabolism MH - Carrier Proteins/*metabolism MH - Ependymoglial Cells/metabolism/*pathology MH - Fibroblast Growth Factor 2/*metabolism MH - Fluorescent Antibody Technique, Indirect MH - Glial Fibrillary Acidic Protein/*metabolism MH - Gliosis/metabolism/*pathology MH - Glutamate-Ammonia Ligase/*metabolism MH - In Situ Nick-End Labeling MH - Organ Culture Techniques MH - Rats MH - Rats, Sprague-Dawley MH - Up-Regulation OTO - NOTNLM OT - Adult retina OT - GFAP OT - Muller cells OT - pre-gliotic OT - retinal explants OT - retinal injury EDAT- 2014/12/17 06:00 MHDA- 2016/07/07 06:00 CRDT- 2014/12/16 06:00 PHST- 2014/12/16 06:00 [entrez] PHST- 2014/12/17 06:00 [pubmed] PHST- 2016/07/07 06:00 [medline] AID - 10.3109/02713683.2014.988360 [doi] PST - ppublish SO - Curr Eye Res. 2015;40(12):1245-60. doi: 10.3109/02713683.2014.988360. Epub 2014 Dec 11.