Neurotrophins involved in neuroprotective antibody effect

• Published in: Acta ophthalmologica (Oxford, England) England), 2017-09, Vol.95 (S259), p.n/a
• Main Authors: Bell, K., Wilding, C., Beck, S., Pfeiffer, N., Grus, F.H.
• Format: Article
• Language: English
• Subjects: 14-3-3 protein; Antibodies; Brain-derived neurotrophic factor; Conditioning; Explants; Fibroblast growth factor 2; Glaucoma; Glial fibrillary acidic protein; Glutamate-ammonia ligase; Glutamine; Glutathione; Interleukin 6; Myoglobins; Neuroprotection; Neurotrophic factors; Neurotrophin 3; Proteins; Retina; Retinal ganglion cells; Synuclein
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/j.1755-3768.2017.03522

Summary Lower levels of different antibodies (abs) can be detected in glaucoma. Several have neuroprotective effects on retinal ganglion cells. Indicated by up‐regulation of glutamine synthetase previous studies show that Müller cells (MC) participate in this effect and we aimed to analyse MC participation in more detail. Primary porcine MC incubated with different abs (0.5 μg/ml γ‐synuclein, 1 μg/ml 14‐3‐3 or GFAP abs for 3 h), a control ab (anti‐myoglobin) or without added abs. To win conditioned medium containing secreted proteins MC were incubated with serum‐reduced medium. BDNF, CTNF, IL6, glutathione, neurotrophin 3, ILG1 and bFGF levels were analysed. Organ cultures were incubated with the conditioned media, medium containing 10 ng/ml CNTF or control medium. MC incubated with 14‐3‐3 (p = 0.045) or GFAP (p = 0.031) abs showed increased CNTF secretion. In comparison to control explants (740 rgc/mm2) rgc/mm2 quantification showed a significant increase in explants incubated with GFAP abs (1014 rgc/mm2, p = 0.04) or 14‐3‐3 abs (910 rgc/mm2,p = 0.07) conditioned medium. Control abs had no effect. We conclude that the neuroprotective antibodies also have an indirect effect on rgcs by increasing CNTF secretion and GS in Müller cells.