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Katharina Bell, Corina Wilding, Ines Rosignol, Norbert Pfeiffer, Franz H Grus; Fc Receptors involved in neuroprotective γ- Synuclein antibody transport into retinal Müller cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6143.
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© ARVO (1962-2015); The Authors (2016-present)
Neuroprotective effects of several antibodies (abs) on retinal ganglion cells could be demonstrated in the past. We were able to detect that retinal Müller glial cells play an important role for promoting the neuroprotective antibody effect by showing elevated glutamine synthetase levels as well as increased CNTF secretion when incubated with the abs. We furthermore found that Müller cells internalise the neuroprotective abs. Ab internalisation can take place via different mechanisms. With this project we aimed to better understand the mechanism of ab uptake into Müller cells in context with Fc gamma receptors (FcγR1a) as well as the neonatal Fc receptor (FcRn). These receptors have also been analysed in the context of other neurodegenerative diseases and have been targeted for therapeutic approaches in several other diseases.
Primary Müller cells were isolated from adolescent 3-6 month old pigs using a papain dissociation kit. Immunohistochemical stainings against FcγR1a as well as FcRn were performed. Ab uptake was analysed using fluorophore-labeled neuroprotective antibody against γ- Synuclein. The ab was added to the medium with a final concentration of 1 µg/mL for different incubation times of 0, 5, 15, 30, 60, 120 and 180 mins. Additionally ab uptake into the cells was analysed after blocking the FcγR1a or the FcRn receptor.
The Müller cells showed the expression of FcγR1a and FcRn. Up to 37.5 % of the cells internalised the anti-γ- Synuclein ab. The intensity of the ab uptake peaked after 60 mins incubation time. Ab uptake was influenced by FcγR1a and FcRn blockage, showing significantly less ab internalisation of the anti-γ-Synuclein ab.
Müller cells possess FcγR1a as well as FcRn receptors. These receptors seem to be involved in the uptake of the antibody against γ- Synuclein, but the mechanism needs to be further analysed in greater detail. Little is known about the function and action of FcγR1a and FcRn on Müller glial cells so far.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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