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Occurrence of retinal ganglion cell loss via autophagy and apoptotic pathways in an autoimmune glaucoma model.

07:00 EST 14th January 2020 | BioPortfolio

Summary of "Occurrence of retinal ganglion cell loss via autophagy and apoptotic pathways in an autoimmune glaucoma model."

: 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 7 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 an RGC loss after RGA immunization compared to both control groups. Also, significantly more cleaved caspase 2 RGCs were observed in RGA animals. More caspase 3 and 8 signals were noted in RGA retinas compared to both controls, while no changes were seen in regard to caspase 9. Furthermore, significantly more cleaved caspase 3 cells were detected in RGA animals. We noted an increase of LC3BII and LAMP1 autophagic cells in the RGA group, while no alterations were seen regarding necrotic RIPK3 cells. Autophagic vesicles were observed via transmission electron microscopy. IgG staining revealed significant differences between the RGA group and controls concerning IgG deposits in the ganglion cell layer.: Due 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.

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Name: Current eye research
ISSN: 1460-2202
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Medical and Biotech [MESH] Definitions

INTERNEURONS of the vertebrate RETINA containing two processes. They receive inputs from the RETINAL PHOTORECEPTOR CELLS and send outputs to the RETINAL GANGLION CELLS. The bipolar cells also make lateral connections in the retina with the RETINAL HORIZONTAL CELLS and with the AMACRINE CELLS.

Nerve cells of the RETINA in the pathway of transmitting light signals to the CENTRAL NERVOUS SYSTEM. They include the outer layer of PHOTORECEPTOR CELLS, the intermediate layer of RETINAL BIPOLAR CELLS and AMACRINE CELLS, and the internal layer of RETINAL GANGLION CELLS.

The inner portion of a retinal rod or a cone photoreceptor cell, situated between the PHOTORECEPTOR CONNECTING CILIUM and the synapse with the adjacent neurons (RETINAL BIPOLAR CELLS; RETINAL HORIZONTAL CELLS). The inner segment contains the cell body, the nucleus, the mitochondria, and apparatus for protein synthesis.

The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve.

An autophagy related protein that is similar to UBIQUITIN-ACTIVATING ENZYME E1. It functions in CYTOPLASM to VACUOLE transport (Cvt) and AUTOPHAGY by activating ATG12 PROTEIN for its conjugation with ATG5 PROTEIN, as well as the conjugation of ATG8 FAMILY PROTEINS with phosphatidylethanolamine for ATG8 association to Cvt vesicles and AUTOPHAGOSOME membranes. It is also required for the nitrogen starvation response in yeast, MITOPHAGY; and autophagic cell death induced by CASPASE 8 inhibition.

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