Light-induced cell death of retinal photoreceptors in the absence of p53.
OBJECTIVE
Cell death by apoptosis is essential for normal development and tissue homeostasis, and it is involved also in a variety of pathologic processes. Apoptosis is the final common pathway of photoreceptor cell death in retinal dystrophies and degeneration. So far, little is known about genes regulating apoptosis in the retina. The tumor-suppressor gene product p53 is a potent regulator of apoptosis in numerous systems. However, p53-independent apoptotic pathways also have been described. In this study the authors investigated the role of p53 in the light-induced apoptosis of retinal photoreceptors using mice lacking p53.


METHODS
Free-moving p53-/- and p53+/+ mice were dark adapted and were exposed to 8,500 or 15,000 lux of diffuse, cool, white fluorescent light for 2 hours. Animals were killed before and immediately after light exposure or at 12 hours in darkness after light exposure. Eyes were enucleated and processed for light and electron microscopy and histochemistry (TdT-dUTP terminal nick-end labeling method). Isolated retinas were subjected to the extraction of total retinal DNA. Electroretinogram (ERG) recordings were performed at all time points.


RESULTS
Morphologic, biochemical, histochemical, and ERG analysis showed that the retinas of untreated p53-/- mice and wild-type control mice were structurally and functionally indistinguishable. After exposure to diffuse white fluorescent light, light-induced photoreceptor cell death was analyzed and was found to be the same in both groups of mice.


CONCLUSIONS
These data suggest that light-induced apoptosis of photoreceptors is independent of functional p53.
Marti
A
A
Department of Ophthalmology, University Hospital, Zurich, Switzerland.
Hafezi
F
F
Lansel
N
N
Hegi
M E
ME
Wenzel
A
A
Grimm
C
C
Niemeyer
G
G
Remé
C E
CE
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D004249:DNA Damage / Q000528:radiation effects; D053938:DNA Fragmentation; D004254:DNA Nucleotidyltransferases; D003623:Dark Adaptation; D003856:Deoxyuracil Nucleotides; D004596:Electroretinography; D016158:Genes, p53 / Q000235:genetics; D008027:Light / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010786:Photoreceptor Cells / Q000473:pathology* / Q000503:physiopathology / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000502:physiology*
D003856:Deoxyuracil Nucleotides; D016159:Tumor Suppressor Protein p53; D004254:DNA Nucleotidyltransferases