Light induced apoptosis is accelerated in transgenic retina overexpressing human EAT/mcl-1, an anti-apoptotic bcl-2 related gene

K. Shinoda, Y. Nakamura, K. Matsushita, Kouji Shimoda, Hajime Okita, M. Fukuma, T. Yamada, H. Ohde, Y. Oguchi, J. I. Hata, A. Umezawa

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Abstract

Background/aim - EAT/mcl-1 (EAT), an immediate early gene, functions in a similar way to bcl-2 in neutralising Bax mediated cytotoxicity, suggesting that EAT is a blocker of cell death. The aim of this study was to determine the effect of overexpression of the human EAT gene on light induced retinal cell apoptosis. Methods - EAT transgenic mice incorporating the EF-1α promoter were utilised, and expression of human EAT was detected by RT-PCR. Light damage was induced by raising mice under constant illumination. Two groups of animals, EAT transgenic mice (n=14) and littermates (n=13), were examined by ERG testing and histopathology at regular time points up to 20 weeks of constant light stimulation. Electrophysiological and histopathological findings were evaluated by established systems of arbitrary scoring as scores 0-2 and scores 0-3, respectively. Results - The mean score (SD) of ERG response was significantly lower in EAT transgenic mice (0.79 (0.89)) than in littermates (1.69 (0.48)) (p<0.01). Although the differences between the two survival curves did not reach statistical significance (p=0.1156), the estimated incidence of electrophysiological retinal damage was higher in EAT mice (0.0495/mouse/week; 95% confidence interval (CT) 0.0347-0.0500) than in litter-mates (0. 0199/mouse/week; 95% CT 0.0035-0.0364). The mean scores (SD) for histopathological retinal degeneration were 2.31 (0.63) in littermates and 1.43 (1.22) in EAT transgenic mice (p=0.065). However, Kaplan-Meier curves for histopathological failure in two groups of mice showed that retinal photoreceptor cells were preserved significantly against constant light in the littermate compared with transgenic mice (p=0.0241). The estimated incidence of histopathological retinal damage was 0.0042/mouse/week in the littermates (95% CI 0-0.0120) and 0.04191 mouse/week in the EAT mice (95% CI 0.0286-0.0500). Conclusion - Retinal photoreceptor cell apoptosis under constant light stimulation is likely to be accelerated in transgenic retina overexpressing EAT.

Original languageEnglish
Pages (from-to)1237-1243
Number of pages7
JournalBritish Journal of Ophthalmology
Volume85
Issue number10
DOIs
Publication statusPublished - 2001

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bcl-2 Genes
Retina
Apoptosis
Light
Transgenic Mice
Vertebrate Photoreceptor Cells
Peptide Elongation Factor 1
Retinal Degeneration
Immediate-Early Genes
Incidence
Lighting
Cell Death
Confidence Intervals
Polymerase Chain Reaction
Survival

ASJC Scopus subject areas

  • Ophthalmology

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Light induced apoptosis is accelerated in transgenic retina overexpressing human EAT/mcl-1, an anti-apoptotic bcl-2 related gene. / Shinoda, K.; Nakamura, Y.; Matsushita, K.; Shimoda, Kouji; Okita, Hajime; Fukuma, M.; Yamada, T.; Ohde, H.; Oguchi, Y.; Hata, J. I.; Umezawa, A.

In: British Journal of Ophthalmology, Vol. 85, No. 10, 2001, p. 1237-1243.

Research output: Contribution to journalArticle

Shinoda, K, Nakamura, Y, Matsushita, K, Shimoda, K, Okita, H, Fukuma, M, Yamada, T, Ohde, H, Oguchi, Y, Hata, JI & Umezawa, A 2001, 'Light induced apoptosis is accelerated in transgenic retina overexpressing human EAT/mcl-1, an anti-apoptotic bcl-2 related gene', British Journal of Ophthalmology, vol. 85, no. 10, pp. 1237-1243. https://doi.org/10.1136/bjo.85.10.1237
Shinoda, K. ; Nakamura, Y. ; Matsushita, K. ; Shimoda, Kouji ; Okita, Hajime ; Fukuma, M. ; Yamada, T. ; Ohde, H. ; Oguchi, Y. ; Hata, J. I. ; Umezawa, A. / Light induced apoptosis is accelerated in transgenic retina overexpressing human EAT/mcl-1, an anti-apoptotic bcl-2 related gene. In: British Journal of Ophthalmology. 2001 ; Vol. 85, No. 10. pp. 1237-1243.
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title = "Light induced apoptosis is accelerated in transgenic retina overexpressing human EAT/mcl-1, an anti-apoptotic bcl-2 related gene",
abstract = "Background/aim - EAT/mcl-1 (EAT), an immediate early gene, functions in a similar way to bcl-2 in neutralising Bax mediated cytotoxicity, suggesting that EAT is a blocker of cell death. The aim of this study was to determine the effect of overexpression of the human EAT gene on light induced retinal cell apoptosis. Methods - EAT transgenic mice incorporating the EF-1α promoter were utilised, and expression of human EAT was detected by RT-PCR. Light damage was induced by raising mice under constant illumination. Two groups of animals, EAT transgenic mice (n=14) and littermates (n=13), were examined by ERG testing and histopathology at regular time points up to 20 weeks of constant light stimulation. Electrophysiological and histopathological findings were evaluated by established systems of arbitrary scoring as scores 0-2 and scores 0-3, respectively. Results - The mean score (SD) of ERG response was significantly lower in EAT transgenic mice (0.79 (0.89)) than in littermates (1.69 (0.48)) (p<0.01). Although the differences between the two survival curves did not reach statistical significance (p=0.1156), the estimated incidence of electrophysiological retinal damage was higher in EAT mice (0.0495/mouse/week; 95{\%} confidence interval (CT) 0.0347-0.0500) than in litter-mates (0. 0199/mouse/week; 95{\%} CT 0.0035-0.0364). The mean scores (SD) for histopathological retinal degeneration were 2.31 (0.63) in littermates and 1.43 (1.22) in EAT transgenic mice (p=0.065). However, Kaplan-Meier curves for histopathological failure in two groups of mice showed that retinal photoreceptor cells were preserved significantly against constant light in the littermate compared with transgenic mice (p=0.0241). The estimated incidence of histopathological retinal damage was 0.0042/mouse/week in the littermates (95{\%} CI 0-0.0120) and 0.04191 mouse/week in the EAT mice (95{\%} CI 0.0286-0.0500). Conclusion - Retinal photoreceptor cell apoptosis under constant light stimulation is likely to be accelerated in transgenic retina overexpressing EAT.",
author = "K. Shinoda and Y. Nakamura and K. Matsushita and Kouji Shimoda and Hajime Okita and M. Fukuma and T. Yamada and H. Ohde and Y. Oguchi and Hata, {J. I.} and A. Umezawa",
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T1 - Light induced apoptosis is accelerated in transgenic retina overexpressing human EAT/mcl-1, an anti-apoptotic bcl-2 related gene

AU - Shinoda, K.

AU - Nakamura, Y.

AU - Matsushita, K.

AU - Shimoda, Kouji

AU - Okita, Hajime

AU - Fukuma, M.

AU - Yamada, T.

AU - Ohde, H.

AU - Oguchi, Y.

AU - Hata, J. I.

AU - Umezawa, A.

PY - 2001

Y1 - 2001

N2 - Background/aim - EAT/mcl-1 (EAT), an immediate early gene, functions in a similar way to bcl-2 in neutralising Bax mediated cytotoxicity, suggesting that EAT is a blocker of cell death. The aim of this study was to determine the effect of overexpression of the human EAT gene on light induced retinal cell apoptosis. Methods - EAT transgenic mice incorporating the EF-1α promoter were utilised, and expression of human EAT was detected by RT-PCR. Light damage was induced by raising mice under constant illumination. Two groups of animals, EAT transgenic mice (n=14) and littermates (n=13), were examined by ERG testing and histopathology at regular time points up to 20 weeks of constant light stimulation. Electrophysiological and histopathological findings were evaluated by established systems of arbitrary scoring as scores 0-2 and scores 0-3, respectively. Results - The mean score (SD) of ERG response was significantly lower in EAT transgenic mice (0.79 (0.89)) than in littermates (1.69 (0.48)) (p<0.01). Although the differences between the two survival curves did not reach statistical significance (p=0.1156), the estimated incidence of electrophysiological retinal damage was higher in EAT mice (0.0495/mouse/week; 95% confidence interval (CT) 0.0347-0.0500) than in litter-mates (0. 0199/mouse/week; 95% CT 0.0035-0.0364). The mean scores (SD) for histopathological retinal degeneration were 2.31 (0.63) in littermates and 1.43 (1.22) in EAT transgenic mice (p=0.065). However, Kaplan-Meier curves for histopathological failure in two groups of mice showed that retinal photoreceptor cells were preserved significantly against constant light in the littermate compared with transgenic mice (p=0.0241). The estimated incidence of histopathological retinal damage was 0.0042/mouse/week in the littermates (95% CI 0-0.0120) and 0.04191 mouse/week in the EAT mice (95% CI 0.0286-0.0500). Conclusion - Retinal photoreceptor cell apoptosis under constant light stimulation is likely to be accelerated in transgenic retina overexpressing EAT.

AB - Background/aim - EAT/mcl-1 (EAT), an immediate early gene, functions in a similar way to bcl-2 in neutralising Bax mediated cytotoxicity, suggesting that EAT is a blocker of cell death. The aim of this study was to determine the effect of overexpression of the human EAT gene on light induced retinal cell apoptosis. Methods - EAT transgenic mice incorporating the EF-1α promoter were utilised, and expression of human EAT was detected by RT-PCR. Light damage was induced by raising mice under constant illumination. Two groups of animals, EAT transgenic mice (n=14) and littermates (n=13), were examined by ERG testing and histopathology at regular time points up to 20 weeks of constant light stimulation. Electrophysiological and histopathological findings were evaluated by established systems of arbitrary scoring as scores 0-2 and scores 0-3, respectively. Results - The mean score (SD) of ERG response was significantly lower in EAT transgenic mice (0.79 (0.89)) than in littermates (1.69 (0.48)) (p<0.01). Although the differences between the two survival curves did not reach statistical significance (p=0.1156), the estimated incidence of electrophysiological retinal damage was higher in EAT mice (0.0495/mouse/week; 95% confidence interval (CT) 0.0347-0.0500) than in litter-mates (0. 0199/mouse/week; 95% CT 0.0035-0.0364). The mean scores (SD) for histopathological retinal degeneration were 2.31 (0.63) in littermates and 1.43 (1.22) in EAT transgenic mice (p=0.065). However, Kaplan-Meier curves for histopathological failure in two groups of mice showed that retinal photoreceptor cells were preserved significantly against constant light in the littermate compared with transgenic mice (p=0.0241). The estimated incidence of histopathological retinal damage was 0.0042/mouse/week in the littermates (95% CI 0-0.0120) and 0.04191 mouse/week in the EAT mice (95% CI 0.0286-0.0500). Conclusion - Retinal photoreceptor cell apoptosis under constant light stimulation is likely to be accelerated in transgenic retina overexpressing EAT.

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