Photoreceptor dystrophy in the RCS rat: roles of oxygen, debris, and bFGF.
OBJECTIVE
To examine the roles of oxygen, basic fibroblast growth factor (bFGF), and photoreceptor debris in the photoreceptor dystrophy of the Royal College of Surgeons (RCS) rat.


METHODS
Pups were exposed during the critical period of their development (postnatal day [P] 16-24) and for some days thereafter to hypoxia and hyperoxia. The effects of these exposures on photoreceptor death, debris accumulation in the subretinal space, and the expression of bFGF protein and mRNA by surviving cells were studied.


RESULTS
During the critical period hyperoxia slowed photoreceptor death in a dose-related fashion and decreased bFGF protein levels, whereas hypoxia accelerated death and increased bFGF levels. At the edges of the retina, where photoreceptors survive longest in normoxia, hypoxia had little effect on either photoreceptor death or bFGF protein levels. Oxygen-induced modulation of rates of death could not be related to the accumulation of debris in the subretinal space. After P27, the relationship between oxygen and photoreceptor death changed markedly, hyperoxia no longer delaying and hypoxia no longer accelerating death.


CONCLUSIONS
The death of RCS rat photoreceptors in the period P16 to P27 is precipitated by hypoxia that may result from the accumulation of photoreceptor debris in the subretinal space. This debris, the result of the phagocytotic failure of the retinal pigment epithelium in this strain, lies in the normal pathway of oxygen diffusing to the photoreceptors from the choriocapillaris. During this period the retina responds to hypoxia by increasing expression of a potentially protective protein (bFGF), but hypoxia-induced damage overwhelms any protection provided by this or other mechanisms. Later stages of the dystrophy may not be hypoxia-induced.
Valter
K
K
NSW Retinal Dystrophy Research Centre, Department of Anatomy and Histology, University of Sydney, Australia.
Maslim
J
J
Bowers
F
F
Stone
J
J
D000818:Animals; D016923:Cell Death; D005109:Extracellular Matrix / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000502:physiology*; D019084:Fluorescent Antibody Technique, Indirect; D018496:Hyperoxia / Q000150:complications / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D010100:Oxygen / Q000502:physiology*; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D012160:Retina / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D010100:Oxygen