Occurrence of Retinal Ganglion Cell Loss via Autophagy and Apoptotic Pathways in an Autoimmune Glaucoma Model

6533b871fe1ef96bd12d1982

RESEARCH PRODUCT

Occurrence of Retinal Ganglion Cell Loss via Autophagy and Apoptotic Pathways in an Autoimmune Glaucoma Model

Uwe Wolfrum Tobias Goldmann Sabrina Reinehr H. Burkhard Dick Verena Buschhorn Stephanie C. Joachim Franz H. Grus Ana M. Mueller-buehl

subject

Male Retinal Ganglion Cells Programmed cell death Necrosis genetic structures Glaucoma Apoptosis Autoantigens Retinal ganglion Autoimmune Diseases 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Microscopy Electron Transmission Autophagy medicine Animals Autoantibodies Caspase 8 biology Caspase 3 business.industry Autophagy Lysosome-Associated Membrane Glycoproteins Glaucoma medicine.disease Caspase 9 eye diseases Sensory Systems Rats Disease Models Animal Ophthalmology medicine.anatomical_structure Microscopy Fluorescence Retinal ganglion cell Rats Inbred Lew Apoptosis Immunoglobulin G 030221 ophthalmology & optometry Cancer research biology.protein sense organs Antibody medicine.symptom business Microtubule-Associated Proteins 030217 neurology & neurosurgery

description

In glaucoma, an apoptotic death of retinal ganglion cells (RGCs) has been shown. However, little is known about other cell death mechanisms, like autophagy or necrosis. Therefore, we investigated these mechanisms in addition to antibody deposits in an experimental autoimmune glaucoma model.Rats were immunized with a retinal ganglion cell-layer homogenate (RGA), while controls received sodium chloride. Untreated rats served as natїve group. After seven weeks, retinal cross-sections were stained with antibodies against RGCs (Brn-3a), apoptosis (cleaved caspase 2, cleaved caspase 3 as well as caspase 3, 8, and 9), autophagy (LC3BII and LAMP1), and necrosis (RIPK3) followed by cell counts. Autophagy was additionally visualized via transmission electron microscopy on retinal sections. Antibody deposits were also analyzed.We noted a RGC loss after RGA immunization compared to both control groups. Also, significantly more cleaved caspase 2Due to the novel results from this study, we conclude that IgG antibodies are involved in RGC loss in this model leading to apoptotic and autophagic cell loss. These results could help to develop new therapy strategies for glaucoma patients.

year	journal	country	edition	language
2020-02-03	Current Eye Research

https://doi.org/10.1080/02713683.2020.1716987