Investigating retinal toxicity of tempol in a model of isolated and perfused bovine retina

Januschowski, Kai; Mueller, Sebastian; Dollinger, Rebecca; Schnichels, Sven; Hofmann, Johanna; Spitzer, Martin S.; Bartz-Schmidt, Karl-Ulrich; Szurman, Peter; Thaler, Sebastian

doi:10.1007/s00417-014-2632-4

Cited by 8 publications

(3 citation statements)

References 24 publications

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“…To date, there have been several reports on the various protective effects of Tempol against inflammation or oxidative damage in tissues [12,13]. In particular, Tempol exerts neuroprotective effects in models of traumatic brain injury, ischemic stroke, and Parkinson’s disease because of its ability to penetrate the blood–brain barrier more easily than other antioxidants can [14,15,16]. …”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Tempol against Cisplatin-Induced Ototoxicity

Youn

Kim

et al. 2016

IJMS

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One of the major adverse effects of cisplatin chemotherapy is hearing loss. Cisplatin-induced ototoxicity hampers treatment because it often necessitates dose reduction, which decreases cisplatin efficacy. This study was performed to investigate the effect of Tempol on cisplatin-induced ototoxicity in an auditory cell line, House Ear Institute-Organ of Corti 1 (HEI-OC1). Cultured HEI-OC1 cells were exposed to 30 μM cisplatin for 24 h with or without a 2 h pre-treatment with Tempol. Cell viability was determined using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and apoptotic cells were identified using terminal deoxynucleotidyl transferase dUTP nick end labeling of nuclei (TUNEL) assay and flow cytometry. The effects of Tempol on cisplatin-induced cleaved poly(ADP-ribose) polymerase, cleaved caspase, and mitochondrial inducible nitric oxide synthase expression were evaluated using western blot analysis. Levels of intracellular reactive oxygen species (ROS) were measured to assess the effects of Tempol on cisplatin-induced ROS accumulation. Mitochondria were evaluated by confocal microscopy, and the mitochondrial membrane potential was measured to investigate whether Tempol protected against cisplatin-induced mitochondrial dysfunction. Cisplatin treatment decreased cell viability, and increased apoptotic features and markers, ROS accumulation, and mitochondrial dysfunction. Tempol pre-treatment before cisplatin exposure significantly inhibited all these cisplatin-induced effects. These results demonstrate that Tempol inhibits cisplatin-induced cytotoxicity in HEI-OC1, and could play a preventive role against cisplatin-induced ototoxicity.

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Section: Discussionmentioning

confidence: 99%

Protective Effect of Tempol against Cisplatin-Induced Ototoxicity

Youn

Kim

et al. 2016

IJMS

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“…The retina b-wave amplitude is a very good indicator of the functional integrity of the retina [ 17 ]. The b-wave of the ERG is a particularly sensitive index of retinal injury of the ischemia [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

PhTx3-4, a Spider Toxin Calcium Channel Blocker, Reduces NMDA-Induced Injury of the Retina

Binda

Carayon

Agostini

et al. 2016

Toxins

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The in vivo neuroprotective effect of PhTx3-4, a spider toxin N-P/Q calcium channel blocker, was studied in a rat model of NMDA-induced injury of the retina. NMDA (N-Methyl-d-Aspartate)-induced retinal injury in rats reduced the b-wave amplitude by 62% ± 3.6%, indicating the severity of the insult. PhTx3-4 treatment increased the amplitude of the b-wave, which was almost equivalent to the control retinas that were not submitted to injury. The PhTx3-4 functional protection of the retinas recorded on the ERG also was observed in the neuroprotection of retinal cells. NMDA-induced injury reduced live cells in the retina layers and the highest reduction, 84%, was in the ganglion cell layer. Notably, PhTx3-4 treatment caused a remarkable reduction of dead cells in the retina layers, and the highest neuroprotective effect was in the ganglion cells layer. NMDA-induced cytotoxicity of the retina increased the release of glutamate, reactive oxygen species (ROS) production and oxidative stress. PhTx3-4 treatment reduced glutamate release, ROS production and oxidative stress measured by malondialdehyde. Thus, we presented for the first time evidence of in vivo neuroprotection from NMDA-induced retinal injury by PhTx3-4 (-ctenitoxin-Pn3a), a spider toxin that blocks N-P/Q calcium channels.

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“…S1 E), supporting the availability of the tissue. The bovine retina has been successfully used in studies that focus on protein purification 30 – 32 and immunohistochemical assays 33 – 37 ; however, apart from sparse electroretinogram (ERG) recordings, 38 – 40 the bovine retina was entirely neglected as a model in retinal neuroscience ( Supplementary Fig. S1 E).…”

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confidence: 99%

The Bovine Ex Vivo Retina: A Versatile Model for Retinal Neuroscience

Kralik,

van Wyk,

Leonardon

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose The isolated ex vivo retina is the standard model in retinal physiology and neuroscience. During isolation, the retina is peeled from the retinal pigment epithelium (RPE), which plays a key role in the visual cycle. Here we introduce the choroid-attached bovine retina as an in vivo–like model for retinal physiology. We find that—in the bovine eye—the choroid and retina can be peeled from the sclera as a single thin sheet. Importantly, the retina remains tightly associated with the RPE, which is sandwiched between the retina and the choroid. Furthermore, bovine tissue is readily available and cheap, and there are no ethical concerns related to the use of animals solely for research purposes. Methods We combine multi-electrode array and single-cell patch-clamp recordings to characterize light responses in the choroid-attached bovine ex vivo retina. Results We demonstrate robust and consistent light responses in choroid-attached preparations. Importantly, light responses adapt to different levels of background illumination and rapidly recover from photobleaching. The choroid-attached retina is also thin enough to permit targeted electrophysiological recording from individual retinal neurons using standard differential interference contrast microscopy. We also characterize light responses and membrane properties of bovine retinal ganglion cells and compare data obtained from bovine and murine retinas. Conclusions The choroid-attached retinal model retains the advantages of the isolated retina but with an intact visual cycle and represents a useful tool to elucidate retinal physiology.

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Investigating retinal toxicity of tempol in a model of isolated and perfused bovine retina

Abstract: Although the photoreceptors seem to have a tolerance to high concentrations of tempol, higher intravitreal concentrations than 1 mM should be considered critical.

Cited by 8 publications

References 24 publications

Protective Effect of Tempol against Cisplatin-Induced Ototoxicity

Protective Effect of Tempol against Cisplatin-Induced Ototoxicity

PhTx3-4, a Spider Toxin Calcium Channel Blocker, Reduces NMDA-Induced Injury of the Retina

The Bovine Ex Vivo Retina: A Versatile Model for Retinal Neuroscience

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