Wk. Ju et al., Selective neuronal survival and upregulation of PCNA in the rat inner retina following transient ischemia, J NE EXP NE, 59(3), 2000, pp. 241-250
Citations number
37
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
In this study we investigated the extent and time course of neuronal cell d
eath and the regulation of the proliferating cell nuclear antigen (PCNA) in
the different retinal cell layers following ischemia-reperfusion injury. R
etinal ischemia was induced by controlled elevation of the intraocular pres
sure for a duration of 60 min. Changes in thickness and cell numbers in the
retinal cell layers were analyzed at various time points (1 h to 4 weeks)
after reperfusion. In parallel, apoptotic cell death was determined by the
TUNEL method and the expression of PCNA analyzed by immunocytochemistry. In
addition, we tested whether PCNA is expressed in neurons by double immunoc
ytochemistry.
The reduction in thickness was found to be less pronounced in the inner nuc
lear layer (INL). Correspondingly cell numbers decreased by only 33% in the
inner retina, but by more than 80% in the outer nuclear layer (ONL). Alter
ations in glial cell numbers did not contribute significantly to postischem
ic changes in the INL and ONL as assessed by using immunocytochemical marke
rs for microglial and Muller cells. The time course of cell death determine
d by the TUNEL technique also differed markedly in the retinal layers being
rapid and transient in the inner retina bur delayed and prolonged in the O
NL. PCNA immunoreactivity was undetectable in the normal retina, but was sp
ecifically induced in neurons of the inner retina within 1 h after reperfus
ion and was sustained for at least 4 weeks. We conclude that in contrast to
photoreceptors in the ONL, a significant proportion of inner retinal neuro
ns is resistant to ischemic insult induced by transiently increased intraoc
ular pressure and that PCNA may possibly play a role in the selective posti
schemic survival of these cells.