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Publication : Selective degeneration of central photoreceptors after hyperbaric oxygen in normal and metallothionein-knockout mice.

First Author  Nachman-Clewner M Year  2008
Journal  Invest Ophthalmol Vis Sci Volume  49
Issue  7 Pages  3207-15
PubMed ID  18579766 Mgi Jnum  J:137160
Mgi Id  MGI:3798129 Doi  10.1167/iovs.07-1039
Citation  Nachman-Clewner M, et al. (2008) Selective degeneration of central photoreceptors after hyperbaric oxygen in normal and metallothionein-knockout mice. Invest Ophthalmol Vis Sci 49(7):3207-15
abstractText  PURPOSE: 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.
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