Selective degeneration of central photoreceptors after hyperbaric oxygen in normal and metallothionein-knockout mice.
OBJECTIVE
Metallothioneins (MTs) in the brain and retina are believed to bind metals and reduce free radicals, thereby protecting neurons from oxidative damage. This study was undertaken to investigate whether retinal photoreceptor (PR) cells lacking MTs are more susceptible to hyperbaric oxygen (HBO)-induced cell death in vivo.


METHODS
Wild-type (WT) and MT-knockout (MT-KO) mice lacking metallothionein (MT)-1 and MT-2 were exposed to three atmospheres of 100% oxygen for 3 hours, 3 times per week for 1, 3, or 5 weeks. The control animals were not exposed. Histologic analysis of PR viability was performed by counting rows of nuclei in the outer nuclear layer (ONL). Ultrastructure studies verified PR damage.


RESULTS
HBO exposure produced a major loss of PR cells in the central retinas of WT and MT-KO mice, with no effect on the peripheral retina even at the longest (5 weeks) exposures. The degree of PR damage and cell death increased with duration of HBO exposure. One week of HBO exposure was insufficient to cause PR death, but tissue damage was observed in the inner and outer segments. At 3 weeks, the rows of PR nuclei in the central retina were significantly reduced by 38% in WT and 28% in MT-KO animals. At 5 weeks, PR loss was identical in WT (34%) and MT-KO (34%) animals and was comparable to that in WT at 3 weeks.


CONCLUSIONS
The data suggest that MT-1 and -2 alone are not sufficient for protecting PRs against HBO-induced cell death. The selective degeneration of central PRs may provide clues to mechanisms of oxidative damage in retinal disease.
Nachman-Clewner
Michele
M
College of Biomedical Science, Charles E. Schmidt College of Biomedical Science, Florida Atlantic University, Boca Raton, Florida 33431, USA.
Giblin
Frank J
FJ
Dorey
C Kathleen
CK
Blanks
Robert H I
RH
Dang
Loan
L
Dougherty
Christopher J
CJ
Blanks
Janet C
JC
D000818:Animals; D016923:Cell Death; D002467:Cell Nucleus / Q000473:pathology; D002470:Cell Survival; D004198:Disease Susceptibility; D006931:Hyperbaric Oxygenation / Q000009:adverse effects*; D008668:Metallothionein / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D010786:Photoreceptor Cells / Q000473:pathology; D012162:Retinal Degeneration / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
C491054:Mt2 protein, mouse; C525355:metallothionein-1, mouse; D008668:Metallothionein