Investigative Ophthalmology & Visual Science, Vol 38, 1667-1677, Copyright © 1997 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

Tissue oxygen during a critical developmental period controls the death and survival of photoreceptors

J Maslim, K Valter, R Egensperger, H Hollander and J Stone
Department of Anatomy and Histology, University of Sydney, Australia.

PURPOSE: To study the death of photoreceptors in normally developing and dystrophic retina and to test the role of hypoxia in causing that death. METHODS: Death of photoreceptors was detected in the albino, hooded, and Royal College of Surgeons (RCS) strains of rat, and in the rabbit and cat, using the TUNEL technique. Retinas of selected ages from animals raised normally and those from rat pups raised for periods in hyperoxia (75% oxygen) or hypoxia (10% oxygen) were studied. RESULTS: In all species and strains examined, a naturally occurring wave of photoreceptor death was detected during the last stages of retinal development. In the albino rat, this wave, which began approximately at postnatal day 15 (P15) and peaked at P22, was reduced by hyperoxia and was intensified by hypoxia, producing a "hypoxic dystrophy" of photoreceptors. In the RCS rat, photoreceptor death also commenced at approximately P15 and then proceeded to exhaustion. This degeneration was greatly reduced by hyperoxia. In the RCS rat, hyperoxia was effective in photoreceptor rescue only during a discrete period, from P16 to P22. In the albino rat, the effectiveness of hypoxia in inducing photoreceptor death was much greater between P15 and P21 than at earlier ages, or in the adult. CONCLUSIONS: During a critical period extending approximately from P15 to P22, tissue oxygen levels strongly influence photoreceptor death and survival in dystrophic and normally developing strains of rat. This period is evident in normal development as a period of naturally occurring photoreceptor death and is evident experimentally as a period during which hyperoxia is effective in rescuing dying photoreceptors and during which hypoxia is effective in inducing death of otherwise viable photoreceptors.

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