Dm. Rosenbaum et al., THE ROLE OF THE P53 PROTEIN IN THE SELECTIVE VULNERABILITY OF THE INNER RETINA TO TRANSIENT ISCHEMIA, Investigative ophthalmology & visual science, 39(11), 1998, pp. 2132-2139
PURPOSE. TO determine whether the p53 protein plays a role in the sele
ctive vulnerability of the inner retina to transient ischemia. METHODS
. Transient retinal ischemia was induced using a high intraocular pres
sure (HIOP) model in the Sprague-Dawley rat for 60 minutes. Histopatho
logic outcome was determined 7 days after ischemia. In addition, analy
sis for evidence for apoptosis (TdT-dUTP terminal nick-end label [TUNE
L] staining) and p53 protein expression (immunohistochemistry) was per
formed 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 performe
d 7 days later. RESULTS. At 7 days subsequent to 60 minutes of ischemi
a in the rat, there was marked thinning of the inner retinal layers. T
here were scattered TUNEL-positive cells within the inner retina, peak
ing at 24 to 48 hours and persisting for at least 7 days. p53 immunoch
emistry demonstrated elevated protein levels within the inner retina;
this finding peaked at 24 to 48 hours but was no longer present at 4 d
ays after ischemia. TUNEL staining of the inner retina of the mouse wa
s most prominent 24 hours subsequent to ischemia but persisted at 48 h
ours. Seven days subsequent to 60 minutes of ischemia in the wild-type
and transgenic mice, histopathologic evaluation demonstrated preserva
tion of the retinal histoarchitecture in the heterozygous group compar
ed with the wild-type or homozygous animals. CONCLUSIONS. These data f
urther 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 targe
t for future therapeutic agents in the treatment of disorders of the r
etina where ischemia plays a pathogenetic role.