2-Phenyl-APB-144-Induced Retinal Pigment Epithelium Degeneration and Its Underlying Mechanisms

Hirai, Shinichiro; Kurashima, Hiroaki; Nakamura, Daisuke; Komatsu, Takao; Yasuda, Yuki; Habashita-Obata, Sayo; Ichikawa, Sanae; Katsuta, Osamu; Kohno, Kenji

doi:10.1089/jop.2014.0076

Cited by 2 publications

(5 citation statements)

References 36 publications

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“…To examine the effect of spermidine on retinal function, including the integrity of the BRB (both outer and inner), BRB permeability [ 21 ] and scotopic ERG a- [ 22 ] and b-waves [ 23 , 24 ] were assessed.…”

Section: Resultsmentioning

confidence: 99%

“…ARPE-19 cells were cultured in DMEM/F12 supplemented with 10% FBS, 100 U/mL penicillin, and 100 mg/mL streptomycin in a humidified atmosphere of 95% air and 5% CO 2 at 37°C, as previously described [ 20 , 21 ]. Passage numbers 23–36 were used for the experiments.…”

Section: Methodsmentioning

confidence: 99%

“…The permeability of the blood-retinal barrier (BRB) was evaluated using vitreous fluorophotometry, as previously described [ 21 ]. Rats were anesthetized as described above on days 1, 3, 7, 14, and 28 after the administration of either DPBS or spermidine (10, 20, or 30 nmol/eye).…”

Section: Methodsmentioning

confidence: 99%

“…Scotopic electroretinogram (ERG) data were recorded on days 2, 6, 13, and 27 after the administration of either DPBS or spermidine (10, 20, or 30 nmol/eye), as previously described [ 20 , 21 ]. For these recordings, rats were dark-adapted for at least 30 min.…”

Section: Methodsmentioning

confidence: 99%

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Spermidine Oxidation‐Mediated Degeneration of Retinal Pigment Epithelium in Rats

Ohashi

Kageyama

Shinomiya

et al. 2017

Oxidative Medicine and Cellular Longevity

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Retinal pigment epithelium (RPE) degeneration is a crucial event in dry age-related macular degeneration and gyrate atrophy. The polyamine spermidine has been shown to induce RPE cell death in vitro. The present study aimed to establish a novel in vivo model of spermidine-induced RPE degeneration and to determine whether spermidine-induced RPE cell death involves oxidative mechanisms. In this study, spermidine caused ARPE-19 cell death in a concentration-dependent manner. This effect was prevented by removal of serum from the culture medium or treatment with amine oxidase inhibitors, N-acetylcysteine (NAC), or aldehyde dehydrogenase (ALDH). Intravitreal injection of spermidine into rats significantly increased the permeability of the blood-retinal barrier and decreased the amplitudes of scotopic electroretinogram a- and b-waves. Histological analysis revealed that spermidine induced vacuolation, atrophy, and dropout of RPE cells, leading to the disruption of photoreceptor outer segments. Simultaneous intravitreal administration of NAC and ALDH with spermidine prominently inhibited the functional and morphological changes induced by spermidine. In conclusion, this study demonstrated that the intravitreal administration of spermidine induced RPE cell dysfunction and death followed by photoreceptor degeneration in rats. These effects of spermidine are thought to be mediated by oxidative stress and a toxic aldehyde generated during spermidine oxidation.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Spermidine Oxidation‐Mediated Degeneration of Retinal Pigment Epithelium in Rats

Ohashi

Kageyama

Shinomiya

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…148,149 In vitro, Salubrinal treatment protects trabecular meshwork cells against ER stress 150 and RPE cells against toxins. 151,152 However, we found SAL003 stimulates the ISR and leads to apoptosis of normal fibroblasts cultivated from donor corneas. 123…”

Section: Target Eif2α Phosphatasementioning

confidence: 70%

Targeting the integrated stress response in ophthalmology

Chu

Peterson

Jun

et al. 2021

Current Eye Research

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Purpose: To summarize the Integrated Stress Response (ISR) in the context of ophthalmology, with special interest on the cornea and anterior segment. Results: The ISR is a powerful and conserved signaling pathway that allows for cells to respond to a diverse array of both intracellular and extracellular stressors. The pathway is classically responsible for coordination of the cellular response to amino acid starvation, ultraviolet light, heme dysregulation, viral infection, and unfolded protein. Under normal circumstances, it is considered pro-survival and a necessary mechanism through which protein translation is controlled. However, in cases of severe or prolonged stress the pathway can promote apoptosis, and loss of normal cellular phenotype. The activation of this pathway culminates in the global inhibition of cap-dependent protein translation and the canonical expression of the activating transcription factor 4 (ATF4). Conclusion:The eye is uniquely exposed to ISR responsive stressors due to its environmental exposure and relative isolation from the circulatory system which are necessary for its function. We will discuss how this pathway is critical for the proper function of the tissue, its role in development, as well as how targeting of the pathway could alleviate key aspects of diverse ophthalmic diseases.

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2-Phenyl-APB-144-Induced Retinal Pigment Epithelium Degeneration and Its Underlying Mechanisms

Cited by 2 publications

References 36 publications

Spermidine Oxidation‐Mediated Degeneration of Retinal Pigment Epithelium in Rats

Spermidine Oxidation‐Mediated Degeneration of Retinal Pigment Epithelium in Rats

Targeting the integrated stress response in ophthalmology

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