Neuroprotective effects of the β-carboline abecarnil studied in cultured cortical neurons and organotypic retinal cultures

Ruscher, Karsten; Rzeczinski, Stefan; Thein, Elisabeth; Freyer, Dorette; Victorov, Ilya V.; Lam, Tsun Ip; Dirnagl, Ulrich

doi:10.1016/j.neuropharm.2007.02.006

Cited by 12 publications

(4 citation statements)

References 33 publications

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“…Downregulation of this enzyme, which converts glutamate to glutamine, can contribute to glutamate-induced excitotoxicity, thus creating a self-perpetuating vicious circle between oxidative stress and excitotoxicity. Both organotypic and dissociated retinal cultures have been used as in vitro experimental models of retinal excitotoxicity, addressing both the study of mechanisms [ 137 – 140 ] and the identification of neuroprotective agents [ 85 , 141 – 144 ].…”

Section: Mechanisms Of Diabetic Milieu -Mediatementioning

confidence: 99%

Primary Retinal Cultures as a Tool for Modeling Diabetic Retinopathy: An Overview

Matteucci

Varano

Mallozzi

et al. 2015

BioMed Research International

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Experimental models of diabetic retinopathy (DR) have had a crucial role in the comprehension of the pathophysiology of the disease and the identification of new therapeutic strategies. Most of these studies have been conducted in vivo, in animal models. However, a significant contribution has also been provided by studies on retinal cultures, especially regarding the effects of the potentially toxic components of the diabetic milieu on retinal cell homeostasis, the characterization of the mechanisms on the basis of retinal damage, and the identification of potentially protective molecules. In this review, we highlight the contribution given by primary retinal cultures to the study of DR, focusing on early neuroglial impairment. We also speculate on possible themes into which studies based on retinal cell cultures could provide deeper insight.

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Section: Mechanisms Of Diabetic Milieu -Mediatementioning

confidence: 99%

Primary Retinal Cultures as a Tool for Modeling Diabetic Retinopathy: An Overview

Matteucci

Varano

Mallozzi

et al. 2015

BioMed Research International

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“…For example, rat5 and mouse6 ORCs have been used to investigate axotomy-induced RGC death and the neuroprotective effect of caspase inhibitors. Glutamate and N -methyl- d -aspartate (NMDA) excitotoxicity of RGC layer cells and the neuroprotective effect of NMDA antagonists have also been studied in both rat7 and rabbit8 ORCs.…”

Section: Introductionmentioning

confidence: 99%

The development of human organotypic retinal cultures (HORCs) to study retinal neurodegeneration

Niyadurupola

Sidaway

Osborne

et al. 2010

British Journal of Ophthalmology

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Aims To develop human organotypic retinal cultures (HORCs) to study retinal ganglion cell (RGC) death in response to ischaemic and excitotoxic insults, both known to cause loss of RGCs and proposed as mechanisms involved in glaucomatous retinal neurodegeneration. Methods Human donor eyes were obtained within 24 h post mortem. The retina was isolated and explants cultured using two techniques. THY-1 mRNA (assessed by real-time quantitative PCR) and neuronal nuclei (NeuN) (assessed by immunohistochemistry) were used as markers of RGCs. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). Results The distribution of THY-1 mRNA and NeuN-labelling within the human retina was consistent with the expected distribution of RGCs. Gross morphology and retinal architecture remained stable over a 96 h culture period. THY-1 mRNA and NeuN-labelled RGC layer cells decreased over the culture period, and there was an increase in TUNEL-labelling with time, but HORCs cultured in serum-free DMEM/HamF12 medium were useful for up to 48 h in culture. N-methyl-d-aspartate (10 µM) caused a reduction in THY-1 mRNA by 24 h and decreased the numbers of NeuN-labelled RGC layer neurons by 48 h, suggesting that the loss of THY-1 mRNA was a marker of RGC stress prior to death. Simulated ischaemia (60 min oxygen/glucose deprivation) caused a reduction at 24 h in both THY-1 mRNA and the numbers of NeuN-labelled neurons of HORCs. Conclusion HORCs provide a useful model to investigate RGC insult by neurodegenerative mechanisms that may lead to glaucoma in human eyes

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“…The organotypic culture of mammalian retina has provided an efficient model for the study of retinal biology,1–4 disease therapy,5 and pathophysiology 6–9. Retinal explants can be targeted with gene promoters and viral vectors and have the advantage over single-cell cultures that neural networks are preserved.…”

Section: Introductionmentioning

confidence: 99%

Particle-Mediated Gene Transfection and Organotypic Culture of Postmortem Human Retina

Masri

Lee

Madigan

2019

Trans. Vis. Sci. Tech.

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Purpose Particle-mediated gene transfer has been used in animal models to study the morphology and connectivity of retinal ganglion cells. The aim of the present study was to apply this method to transfect ganglion cells in postmortem human retina. Methods Postmortem human eyes from male and female donors aged 40 to 76 years old were obtained within 15 hours after death. In addition, two marmoset retinas were obtained immediately after death. Ganglion cells were transfected with an expression plasmid for the postsynaptic density 95 protein conjugated to green or yellow fluorescent protein. Retinas were cultured for 3 days, fixed and then processed with immunohistochemical markers to reveal their stratification in the inner plexiform layer. Results The retinas maintained their morphology and immunohistochemical properties for at least 3 days in culture. Bipolar and ganglion cell morphology was comparable to that observed in noncultured tissue. The quality of transfected cells in human retina was similar to that in freshly enucleated marmoset eyes. Based on dendritic field size and stratification, at least 11 morphological types of retinal ganglion cell were distinguished. Conclusions Particle-mediated gene transfer allows efficient targeting of retinal ganglion cells in cultured postmortem human retina. Translational Relevance The translational value of this methodology lies in the provision of an in vitro platform to study structural and connectivity changes in human eye diseases that affect the integrity and organization of cells in the retina.

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Neuroprotective effects of the β-carboline abecarnil studied in cultured cortical neurons and organotypic retinal cultures

Cited by 12 publications

References 33 publications

Primary Retinal Cultures as a Tool for Modeling Diabetic Retinopathy: An Overview

Primary Retinal Cultures as a Tool for Modeling Diabetic Retinopathy: An Overview

The development of human organotypic retinal cultures (HORCs) to study retinal neurodegeneration

Particle-Mediated Gene Transfection and Organotypic Culture of Postmortem Human Retina

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