The role of the p53 protein in the selective vulnerability of the inner retina to transient ischemia

Daniel M. Rosenbaum, Pearl S. Rosenbaum, Himanshu Gupta, Manjeet Singh, Ashim Aggarwal, David H. Hall, Steven Roth, John A. Kessler

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Abstract

PURPOSE. To determine whether the p53 protein plays a role in the selective vulnerability of the inner retina to transient ischemia. METHODS. Transient retinal ischemia was induced using a high intraocular pressure (HIOP) model in the Sprague-Dawley rat for 60 minutes. Histopathologic outcome was determined 7 days after ischemia. In addition, analysis for evidence for apoptosis (TdT-dUTP terminal nick-end label [TUNEL] staining) and p53 protein expression (immunohistochemistry) was performed at several points during the reperfusion period. In a separate set of experiments, wild- type mice and two groups of transgenic mice, one homozygous and the other heterozygous for the p53 null gene, were also subjected to HIOP for 60 minutes, and histopathology was performed 7 days later. RESULTS. At 7 days subsequent to 60 minutes of ischemia in the rat, there was marked thinning of the inner retinal layers. There were scattered TUNEL-positive cells within the inner retina, peaking at 24 to 48 hours and persisting for at least 7 days. p53 immunochemistry demonstrated elevated protein levels within the inner retina; this finding peaked at 24 to 48 hours but was no longer present at 4 days after ischemia. TUNEL staining of the inner retina of the mouse was most prominent 24 hours subsequent to ischemia but persisted at 48 hours. Seven days subsequent to 60 minutes of ischemia in the wild-type and transgenic mice, histopathologic evaluation demonstrated preservation of the retinal histoarchitecture in the heterozygous group compared with the wildtype or homozygous animals. CONCLUSIONS. These data further support the hypothesis that the delayed cell death that occurs after transient retinal ischemia is, in part, apoptotic. In addition, they suggest a role for the p53 protein in the selective vulnerability of the inner retina to transient ischemia. p53 protein may be a target for future therapeutic agents in the treatment of disorders of the retina where ischemia plays a pathogenetic role.

Original languageEnglish (US)
Pages (from-to)2132-2139
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume39
Issue number11
StatePublished - Oct 1998

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Retina
Ischemia
Proteins
Intraocular Pressure
Transgenic Mice
Staining and Labeling
Immunochemistry
p53 Genes
Reperfusion
Sprague Dawley Rats
Cell Death
Immunohistochemistry
Apoptosis
Therapeutics

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Rosenbaum, D. M., Rosenbaum, P. S., Gupta, H., Singh, M., Aggarwal, A., Hall, D. H., ... Kessler, J. A. (1998). The role of the p53 protein in the selective vulnerability of the inner retina to transient ischemia. Investigative Ophthalmology and Visual Science, 39(11), 2132-2139.

The role of the p53 protein in the selective vulnerability of the inner retina to transient ischemia. / Rosenbaum, Daniel M.; Rosenbaum, Pearl S.; Gupta, Himanshu; Singh, Manjeet; Aggarwal, Ashim; Hall, David H.; Roth, Steven; Kessler, John A.

In: Investigative Ophthalmology and Visual Science, Vol. 39, No. 11, 10.1998, p. 2132-2139.

Research output: Contribution to journalArticle

Rosenbaum, DM, Rosenbaum, PS, Gupta, H, Singh, M, Aggarwal, A, Hall, DH, Roth, S & Kessler, JA 1998, 'The role of the p53 protein in the selective vulnerability of the inner retina to transient ischemia', Investigative Ophthalmology and Visual Science, vol. 39, no. 11, pp. 2132-2139.
Rosenbaum, Daniel M. ; Rosenbaum, Pearl S. ; Gupta, Himanshu ; Singh, Manjeet ; Aggarwal, Ashim ; Hall, David H. ; Roth, Steven ; Kessler, John A. / The role of the p53 protein in the selective vulnerability of the inner retina to transient ischemia. In: Investigative Ophthalmology and Visual Science. 1998 ; Vol. 39, No. 11. pp. 2132-2139.
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abstract = "PURPOSE. To determine whether the p53 protein plays a role in the selective vulnerability of the inner retina to transient ischemia. METHODS. Transient retinal ischemia was induced using a high intraocular pressure (HIOP) model in the Sprague-Dawley rat for 60 minutes. Histopathologic outcome was determined 7 days after ischemia. In addition, analysis for evidence for apoptosis (TdT-dUTP terminal nick-end label [TUNEL] staining) and p53 protein expression (immunohistochemistry) was performed at several points during the reperfusion period. In a separate set of experiments, wild- type mice and two groups of transgenic mice, one homozygous and the other heterozygous for the p53 null gene, were also subjected to HIOP for 60 minutes, and histopathology was performed 7 days later. RESULTS. At 7 days subsequent to 60 minutes of ischemia in the rat, there was marked thinning of the inner retinal layers. There were scattered TUNEL-positive cells within the inner retina, peaking at 24 to 48 hours and persisting for at least 7 days. p53 immunochemistry demonstrated elevated protein levels within the inner retina; this finding peaked at 24 to 48 hours but was no longer present at 4 days after ischemia. TUNEL staining of the inner retina of the mouse was most prominent 24 hours subsequent to ischemia but persisted at 48 hours. Seven days subsequent to 60 minutes of ischemia in the wild-type and transgenic mice, histopathologic evaluation demonstrated preservation of the retinal histoarchitecture in the heterozygous group compared with the wildtype or homozygous animals. CONCLUSIONS. These data further support the hypothesis that the delayed cell death that occurs after transient retinal ischemia is, in part, apoptotic. In addition, they suggest a role for the p53 protein in the selective vulnerability of the inner retina to transient ischemia. p53 protein may be a target for future therapeutic agents in the treatment of disorders of the retina where ischemia plays a pathogenetic role.",
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N2 - PURPOSE. To determine whether the p53 protein plays a role in the selective vulnerability of the inner retina to transient ischemia. METHODS. Transient retinal ischemia was induced using a high intraocular pressure (HIOP) model in the Sprague-Dawley rat for 60 minutes. Histopathologic outcome was determined 7 days after ischemia. In addition, analysis for evidence for apoptosis (TdT-dUTP terminal nick-end label [TUNEL] staining) and p53 protein expression (immunohistochemistry) was performed at several points during the reperfusion period. In a separate set of experiments, wild- type mice and two groups of transgenic mice, one homozygous and the other heterozygous for the p53 null gene, were also subjected to HIOP for 60 minutes, and histopathology was performed 7 days later. RESULTS. At 7 days subsequent to 60 minutes of ischemia in the rat, there was marked thinning of the inner retinal layers. There were scattered TUNEL-positive cells within the inner retina, peaking at 24 to 48 hours and persisting for at least 7 days. p53 immunochemistry demonstrated elevated protein levels within the inner retina; this finding peaked at 24 to 48 hours but was no longer present at 4 days after ischemia. TUNEL staining of the inner retina of the mouse was most prominent 24 hours subsequent to ischemia but persisted at 48 hours. Seven days subsequent to 60 minutes of ischemia in the wild-type and transgenic mice, histopathologic evaluation demonstrated preservation of the retinal histoarchitecture in the heterozygous group compared with the wildtype or homozygous animals. CONCLUSIONS. These data further support the hypothesis that the delayed cell death that occurs after transient retinal ischemia is, in part, apoptotic. In addition, they suggest a role for the p53 protein in the selective vulnerability of the inner retina to transient ischemia. p53 protein may be a target for future therapeutic agents in the treatment of disorders of the retina where ischemia plays a pathogenetic role.

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