The limits of oxygen rescue of cell death in developing retina

Abstract

Purpose. The demonstration that hyperoxia rescues photoreceptors, which die in the retina both during normal development and, more massively, in the dystrophic rcs rat, led us to explore the limits of oxygen rescue. Methods. Albino and rcs rats were raised with the mothers from birth to up to several weeks age. Some were exposed to hyperoxia, being placed with the mother into perspex chambers in which the atmosphere contained 70-75% oxygen, for periods of up to 13 days. After euthanasia by overdose of sodium pentobarbitone by i.p. injection, the eyes were fixed in 4% paraformaldehyde, frozen-sectioned at 15μm and labelled with the TUNEL technique, which demonstrates fragmenting DNA, and/or with the lectin G. simplicifolia , which labels blood vessels and microglia. Results. We confirmed the high level of rescue of photoreceptors reported in an accompanying abstract, when hyperoxia was delivered from P16 through P24. A similar level of rescue was obtained when hyperoxia was delivered from P16 through P20. However, when hyperoxia commenced at P20 (for 4d), rescue was only 40%; and when commenced at P22 (for 13 d) and P25 (for 4 d) was 0%. In addition, an attempt was made to rescue cells dying in the inner nuclear layer, where cell death peaks at P10. Hyperoxia from P6 through P10 did not reduce death in any of the sublayers of the INL. Conclusion. Hyperoxic rescue of rat photoreceptors appears possible only in photoreceptors, and only during a window of opportunity, from P16 through P21. If these findings prove general to other species they will be relevant to the understanding of human photoreceptor dystrophies (retinitis pigmentosa). Show more