PEDF counteracts DL-α-aminoadipate toxicity and rescues gliotoxic damages in RPE-free chicken retinal explants.

Publisher: Academic Press Country of Publication: England NLM ID: 0370707 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0007 (Electronic) Linking ISSN: 00144835 NLM ISO Abbreviation: Exp Eye Res Subsets: MEDLINE

Publication: London : Academic Press
Original Publication: London.

2-Aminoadipic Acid/*toxicity ; Ependymoglial Cells/*drug effects ; Excitatory Amino Acid Antagonists/*toxicity ; Eye Proteins/*pharmacology ; Gliosis/*prevention & control ; Nerve Growth Factors/*pharmacology ; Retina/*embryology ; Serpins/*pharmacology; Acetylcholine/metabolism ; Acetylcholinesterase/metabolism ; Animals ; Apoptosis/drug effects ; Caspase 3/metabolism ; Chick Embryo ; Ependymoglial Cells/metabolism ; Glial Fibrillary Acidic Protein/metabolism ; Gliosis/metabolism ; Gliosis/pathology ; Immunohistochemistry ; In Situ Nick-End Labeling ; Organ Culture Techniques ; Oxidative Stress ; Retina/drug effects ; Retinal Pigment Epithelium/cytology ; Reverse Transcriptase Polymerase Chain Reaction

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.
(Copyright © 2015 Elsevier Ltd. All rights reserved.)

Keywords: Gliosis; IPL subband; Inner plexiform layer; Müller glial cell; Photoreceptor; Radial glia

0 (Excitatory Amino Acid Antagonists)
0 (Eye Proteins)
0 (Glial Fibrillary Acidic Protein)
0 (Nerve Growth Factors)
0 (Serpins)
0 (pigment epithelium-derived factor)
1K7B1OED4N (2-Aminoadipic Acid)
EC 3.1.1.7 (Acetylcholinesterase)
EC 3.4.22.- (Caspase 3)
N9YNS0M02X (Acetylcholine)

Date Created: 20150218 Date Completed: 20150720 Latest Revision: 20150508

20231215

10.1016/j.exer.2015.02.010

25686916