Regulation by oxygen of photoreceptor death in the developing and adult C57BL/6J mouse.
We have examined the role of tissue oxygen in the regulation of photoreceptor death in the C57BL/6J mouse. Litters of C57BL/6J mice were raised in dim cyclic (12 hr dark, 12 hr 50 lx) light. Adults or litters aged P7 or P8 were placed with their mothers in plexiglass chambers in which oxygen levels were set at 21% (normoxic), 10 or 11% (hypoxic) or 70% (hyperoxic) for up to 22 days. At intervals after introduction to these chambers, retinas were examined for cell death, using the TUNEL technique. Hypoxia accelerated cell death up to five-fold during a critical developmental period from approximately P12 to 18. Thereafter hypoxia-induced cell death declined rapidly. Hyperoxia slowed photoreceptor death over the same period, to approximately half control levels. At the anterior edge of the developing retina the effects of hypoxia and hyperoxia differed markedly from the rest of the retina. In the adult, hypoxia accelerated photoreceptor death, but the acceleration was an order of magnitude weaker than during the critical period of developing retina. Hypoxia-induced photoreceptor death remained above control levels after 20 days exposure. Results suggest that the naturally occurring wave of photoreceptor death seen in developing mouse retina during their development (P12-P20) is regulated by a physiological episode of hypoxia. After P20, photoreceptor vulnerability to hypoxia falls to a low but significant level. The edge of the retina appears subject to chronic hyperoxic stress from P14 into adulthood. Tissue oxygen levels are important determinants of photoreceptor death and survival in both developing and adult retina.
Mervin
Kyle
K
NSW Retinal Dystrophy Research Centre, Department of Anatomy and Histology, University of Sydney, Sydney 2006, Australia. kyle@anatomy.usyd.edu.au
Stone
Jonathan
J
D000375:Aging / Q000473:pathology* / Q000502:physiology; D000818:Animals; D016923:Cell Death / Q000502:physiology; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D010101:Oxygen Consumption / Q000502:physiology*; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology*; D012160:Retina / Q000254:growth & development