RGMA and neogenin protein expression are influenced by lens injury following optic nerve crush in the rat retina

Schnichels, Sven; Heiduschka, Peter; Julien, Sylvie

doi:10.1007/s00417-011-1791-9

Cited by 10 publications

(6 citation statements)

References 61 publications

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“…The specificity of the RGMa and Neogenin antibodies has been confirmed previously using immunocytochemical, immunohistochemical and/or Western blot methods on transfected cells and endogenous tissues [38], [60]–[63]. Here, the specificity of the anti-RGM and anti-Neogenin antibodies was further tested by immunocytochemistry (Fig.…”

Section: Resultssupporting

confidence: 72%

“…In brief, sections were washed in PBS (pH 7.4) and incubated in normal blocking buffer (PBS, 4% BSA and 0.1% Triton) for 1 hr at RT and incubated with goat anti-RGMa antibody (AF2458; R&D systems) 1∶200, sheep anti-RGMb antibody (AF3597; R&D systems) 1∶200 or goat anti-Neogenin antibody (AF1079; R&D systems) 1∶200 overnight in normal blocking buffer at 4°C. The specificity of the RGMa and Neogenin antibodies has been confirmed previously using immunocytochemical, immunohistochemical and/or Western blot methods on transfected cells and endogenous tissues [38], [60]–[63]. As a control, sections were incubated with immunoglobulin isotype controls matching the RGM or Neogenin antibodies (AB-108-C, 5-001-A; R&D systems).…”

Section: Methodsmentioning

confidence: 79%

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Spatiotemporal Expression of Repulsive Guidance Molecules (RGMs) and Their Receptor Neogenin in the Mouse Brain

2013

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Neogenin has been implicated in a variety of developmental processes such as neurogenesis, neuronal differentiation, apoptosis, migration and axon guidance. Binding of repulsive guidance molecules (RGMs) to Neogenin inhibits axon outgrowth of different neuronal populations. This effect requires Neogenin to interact with co-receptors of the uncoordinated locomotion-5 (Unc5) family to activate downstream Rho signaling. Although previous studies have reported RGM, Neogenin, and/or Unc5 expression, a systematic comparison of RGM and Neogenin expression in the developing nervous system is lacking, especially at later developmental stages. Furthermore, information on RGM and Neogenin expression at the protein level is limited. To fill this void and to gain further insight into the role of RGM-Neogenin signaling during mouse neural development, we studied the expression of RGMa, RGMb, Neogenin and Unc5A-D using in situ hybridization, immunohistochemistry and RGMa section binding. Expression patterns in the primary olfactory system, cortex, hippocampus, habenula, and cerebellum were studied in more detail. Characteristic cell layer-specific expression patterns were detected for RGMa, RGMb, Neogenin and Unc5A-D. Furthermore, strong expression of RGMa, RGMb and Neogenin protein was found on several major axon tracts such as the primary olfactory projections, anterior commissure and fasciculus retroflexus. These data not only hint at a role for RGM-Neogenin signaling during the development of different neuronal systems, but also suggest that Neogenin partners with different Unc5 family members in different systems. Overall, the results presented here will serve as a framework for further dissection of the role of RGM-Neogenin signaling during neural development.

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Section: Resultssupporting

confidence: 72%

Section: Methodsmentioning

confidence: 79%

Spatiotemporal Expression of Repulsive Guidance Molecules (RGMs) and Their Receptor Neogenin in the Mouse Brain

2013

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“…When neogenin is unbound to its ligand, it can act as a dependence receptor by directly inducing cell death via proteolytic cleavage of its intracellular domain in order to expose a caspase activation site (38). Electroporation of a noncleavable form of neogenin compared with the WT form resulted in significantly reduced death, suggest-trasted with the nondiseased human retina, where neogenin photoreceptor expression was very low, similar to what was seen both in WT adult rat (35) and the WT mouse retina ( Figure 1C). Neogenin mediates photoreceptor death in RP mice.…”

Section: The Journal Of Clinical Investigation R E S E a R C H A R T mentioning

confidence: 55%

Neogenin neutralization prevents photoreceptor loss in inherited retinal degeneration

Charish¹,

Shabanzadeh²,

Chen³

et al. 2020

Journal of Clinical Investigation

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“…In most of these models, the IOP is surgically increased by laser-induced damage or microbead injection (Zhang et al, 2017;Calkins et al, 2018;de Hoz et al, 2018). Other glaucoma models are optic nerve crush or axotomy (Schnichels et al, 2012b;Donahue et al, 2019). Although acute optic nerve damage models are often not suitable to mimic chronic glaucoma, they are useful to evaluate RGC pathogenesis and neuroregeneration (Nadal-Nicolás et al, 2017).…”

Section: Glaucomamentioning

confidence: 99%

Organ Cultures for Retinal Diseases

et al. 2020

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The successful development of novel therapies is closely linked with understanding the underlying pathomechanisms of a disease. To do so, model systems that reflect human diseases and allow for the evaluation of new therapeutic approaches are needed. Yet, preclinical animal studies often have limited success in predicting human physiology, pathology, and therapeutic responses. Moreover, animal testing is facing increasing ethical and bureaucratic hurdles, while human cell cultures are limited in their ability to represent in vivo situations due to the lack of the tissue microenvironment, which may alter cellular responses. To overcome these struggles, organ cultures, especially those of complex organs such as the retina, can be used to study physiological reactions to substances or stressors. Human and animal organ cultures are now well established and recognized. This mini-review discusses how retinal organ cultures can be used to preserve tissue architecture more realistically and therefore better represent disease-related changes. It also shows how molecular biological, biochemical, and histological techniques can be combined to investigate how anatomical localization may alter cellular responses. Examples for the use of retinal organ cultures, including models to study age-related macular degeneration (AMD), retinitis pigmentosa (RP), central artery occlusion (CRAO), and glaucoma are presented, and their advantages and disadvantages are discussed. We conclude that organ cultures significantly improve our understanding of complex retinal diseases and may advance treatment testing without the need for animal testing.

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RGMA and neogenin protein expression are influenced by lens injury following optic nerve crush in the rat retina

Cited by 10 publications

References 61 publications

Spatiotemporal Expression of Repulsive Guidance Molecules (RGMs) and Their Receptor Neogenin in the Mouse Brain

Spatiotemporal Expression of Repulsive Guidance Molecules (RGMs) and Their Receptor Neogenin in the Mouse Brain

Neogenin neutralization prevents photoreceptor loss in inherited retinal degeneration

Organ Cultures for Retinal Diseases

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