Thangaraj, Gopenath ; Christophel, Jeanette ; Bachmann, Gesine ; Greif, Alexander ; Layer, Paul G. (2015)
PEDF counteracts DL-α-aminoadipate toxicity and rescues gliotoxic damages in RPE-free chicken retinal explants.
In: Experimental eye research, 134
doi: 10.1016/j.exer.2015.02.010
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
Gliotoxic responses complicate human eye diseases, the causes of which often remain obscure. Here, we activated Müller cells (MCs) by the gliotoxin DL-α-aminoadipate (AAA) and assayed possible protective effects by pigment epithelium-derived factor (PEDF) in RPE-free retinal explants of the E6 chick embryo. These models are suited to analyze gliotoxic reactions in vitro, since the avian retina contains only Müller cells (MCs) as glial components, and the RPE-free explants are devoid of a major PEDF source. ChAT- and AChE-immunohistochemistry (IHC) revealed that AAA treatment disrupted the differentiation of cholinergic amacrine cells in the inner plexiform layer. At the applied concentration of 1 mM AAA, apoptosis of MCs was slightly increased, as shown by TUNEL and caspase-3 activity assays. Concomitantly, cell-free gaps emerged in the middle of the retina, where MCs were swollen and amassed glutamine synthetase (shown by GS and Vimentin IHC). AAA treatment strongly activated MCs, as shown by GFAP IHC, and by an increase of stress-related catalase activity. Remarkably, nearly all effects of AAA on MCs were effectively counter-balanced by 50 ng/ml PEDF co-treatment, as also shown by RT-PCR. These findings suggest that supplementation with PEDF can protect the retina against gliotoxic attacks. Further studies should establish whether PEDF similarly protects a gliotoxic human retina.
Typ des Eintrags: | Artikel |
---|---|
Erschienen: | 2015 |
Autor(en): | Thangaraj, Gopenath ; Christophel, Jeanette ; Bachmann, Gesine ; Greif, Alexander ; Layer, Paul G. |
Art des Eintrags: | Bibliographie |
Titel: | PEDF counteracts DL-α-aminoadipate toxicity and rescues gliotoxic damages in RPE-free chicken retinal explants. |
Sprache: | Englisch |
Publikationsjahr: | 2015 |
Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Experimental eye research |
Jahrgang/Volume einer Zeitschrift: | 134 |
DOI: | 10.1016/j.exer.2015.02.010 |
Kurzbeschreibung (Abstract): | Gliotoxic responses complicate human eye diseases, the causes of which often remain obscure. Here, we activated Müller cells (MCs) by the gliotoxin DL-α-aminoadipate (AAA) and assayed possible protective effects by pigment epithelium-derived factor (PEDF) in RPE-free retinal explants of the E6 chick embryo. These models are suited to analyze gliotoxic reactions in vitro, since the avian retina contains only Müller cells (MCs) as glial components, and the RPE-free explants are devoid of a major PEDF source. ChAT- and AChE-immunohistochemistry (IHC) revealed that AAA treatment disrupted the differentiation of cholinergic amacrine cells in the inner plexiform layer. At the applied concentration of 1 mM AAA, apoptosis of MCs was slightly increased, as shown by TUNEL and caspase-3 activity assays. Concomitantly, cell-free gaps emerged in the middle of the retina, where MCs were swollen and amassed glutamine synthetase (shown by GS and Vimentin IHC). AAA treatment strongly activated MCs, as shown by GFAP IHC, and by an increase of stress-related catalase activity. Remarkably, nearly all effects of AAA on MCs were effectively counter-balanced by 50 ng/ml PEDF co-treatment, as also shown by RT-PCR. These findings suggest that supplementation with PEDF can protect the retina against gliotoxic attacks. Further studies should establish whether PEDF similarly protects a gliotoxic human retina. |
Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Developmental Biology and Neurogenetics |
Hinterlegungsdatum: | 25 Feb 2015 08:53 |
Letzte Änderung: | 11 Jun 2015 11:57 |
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