September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Improved neuronal survival after intravitreal injection of an α-synuclein antibody in a glaucoma animal model
Author Affiliations & Notes
  • Julia Teister
    Ophthalmology, University Medical Center, Mainz , Mainz, Germany
  • Fabian Anders
    Ophthalmology, University Medical Center, Mainz , Mainz, Germany
  • Verena Prokosch
    Ophthalmology, University Medical Center, Mainz , Mainz, Germany
  • Sabine Beck
    Ophthalmology, University Medical Center, Mainz , Mainz, Germany
  • Sebastian Funke
    Ophthalmology, University Medical Center, Mainz , Mainz, Germany
  • Caroline Manicam
    Ophthalmology, University Medical Center, Mainz , Mainz, Germany
  • Adrian Gericke
    Ophthalmology, University Medical Center, Mainz , Mainz, Germany
  • Norbert Pfeiffer
    Ophthalmology, University Medical Center, Mainz , Mainz, Germany
  • Franz H Grus
    Ophthalmology, University Medical Center, Mainz , Mainz, Germany
  • Footnotes
    Commercial Relationships   Julia Teister, None; Fabian Anders, None; Verena Prokosch, None; Sabine Beck, None; Sebastian Funke, None; Caroline Manicam, None; Adrian Gericke, None; Norbert Pfeiffer, None; Franz Grus, None
  • Footnotes
    Support  Focus Program Translational Neurosciences (FTN) of the Johannes Gutenberg University Mainz
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Julia Teister, Fabian Anders, Verena Prokosch, Sabine Beck, Sebastian Funke, Caroline Manicam, Adrian Gericke, Norbert Pfeiffer, Franz H Grus; Improved neuronal survival after intravitreal injection of an α-synuclein antibody in a glaucoma animal model. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : Glaucoma is a neurodegenerative disease, leading to retinal ganglion cell (RGC) and axonal loss. The pathogenesis includes alterations in autoantibody (Aab) profiles, as altered Aab levels were observed in sera of glaucoma patients. One of those candidates is α-synuclein Aab. The purpose of this study was to identify the role of α-synuclein Aab in the pathogenesis of glaucoma and its impact on neuronal survival.

Methods : Intraocular pressure (IOP) was elevated in Sprague Dawley rats (n=14) by cauterization of 3 episcleral veins. Intravitreal injection (IVI) was given once 3 weeks after cauterization. Fellow eyes served as (1) normotensive controls (n=14) and were compared to IOP elevated eyes of (2) controls (n=3, no IVI), (3) buffer (n=6, IVI of buffer), and (4) α-synuclein Aab (n=5, IVI of 25 µg α-synuclein antibody). IOP was recorded weekly. Nerve fibre layer thickness (NFLT) after IVI was set in relation to NFLT at the end of the study using optical coherence tomography. After 8 weeks of follow-up animals were sacrificed and optic nerves and retinae were collected for PPD- and Brn3a staining. Analysis was performed double-blind and data is presented as mean±SD.

Results : Episcleral vein cauterization increased IOP significantly to 17.8±1.1 mmHg compared to fellow eyes with 11.3±0.4 mmHg (p<0.01). The NFLT of fellow eyes did not change (100.6±2.0%), while it was reduced to 90.1±1.5% (p<0.01) in controls, to 87.2±2.2% (p<0.01) in buffer group and only to 96.6±2.6% (p=0.14) in α-synuclein Aab group at the end of the study. Axon density/mm2 showed a decay to 322477±37055 (p<0.01) in controls, 307787±28399 (p<0.01) in buffer group, and 399818±16529 (p=0.19) in the α-synuclein Aab group compared to fellow eyes with 439529±18161 axons/mm2. The RGC density/mm2 was reduced to 1076±132 (p<0.05) in controls, 1068±163 (p<0.01) in buffer group and 1252±95 (p=0.08) in α-synuclein Aab group compared to fellow eyes with 1516±186 RGC/mm2. Immunohistochemical staining of retina against the α-synuclein Aab revealed binding of the antibody within the RGC layer.

Conclusions : The IVI of buffer had no impact on neuronal loss compared to controls without injection. The results of this study indicate that α-synuclein antibodies improve neuronal survival in the optic nerve and the retina in an experimental glaucoma animal model and might therefore be a new approach to glaucoma therapy.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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