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A.L. Dorfman, N. Cuenca, I. Pinilla, S. Joly, S. Chemtob, P. Lachapelle; Retinal Cytoarchitectural Anomalies Following Postnatal Hyperoxia: More Than What Originally Met The Eye . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3084.
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© ARVO (1962-2015); The Authors (2016-present)
We have previously shown that postnatal hyperoxia causes destruction of the plexiform layers in rats along with significant electroretinographic anomalies. The purpose of this study was to identify the mechanisms at the origin of this loss.
Sprague Dawley (SD) and Long Evans (LE) rats were exposed to hyperoxia (n=24 control, 42 exposed) as previously described from birth to P6 or P14 following which the rats were perfused, either at time of removal from 80% O2 (at P6 or P14), or at P60. 10µm thick cryosections were collected for analysis.
At P60, synaptophysin (presynaptic marker) staining confirms the lack of functional synaptic terminals in the OPL of SD and in the OPL and IPL of LE rats. Uneven staining of ON–bipolar cell terminals with mGluR6 suggests that they contribute to OPL thinning. To further distinguish between rod and cone ON–bipolar cells, PKC (rods) and recoverin (cone) stainings were used and both showed a lack of dendritic terminals in the OPL with disorganized axonal projections in the IPL. Calbindin staining also revealed a reduction in the number of horizontal cells. Although photoreceptor cell bodies appeared intact, a decrease in bassoon staining (in rod and cone synaptic ribbon terminals) suggests limited communication to the inner retina. All of the above findings were significantly more pronounced in LE compared to SD rats. Furthermore, TUNEL positive profiles in LE rats were located in both the INL and ONL [75.1% and 47.9% respectively, compared to control (p<0.05)] while cell death was limited to the INL of SD rats (47.5%, p<0.05).
Our results suggest that cell death and synaptic retraction are at the root of plexiform layer thinning. The increased number of TUNEL positive cells in the nuclear layers confirms that these cells die, at least in part, due to apoptosis and that LE rats are more susceptible than SD rats. Finally, our results point to the inner retina as the primary target of hyperoxic injury, followed by damage to the outer retina (to a lesser extent). Our findings propose a previously undescribed mechanism of cell death and synaptic retraction that are most probably at the origin of the functional consequences of hyperoxia.
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