Photoreceptor cell apoptosis in the retinal degeneration of Uchl3-deficient mice

Yae Sano, Akiko Furuta, Rieko Setsuie, Hisae Kikuchi, Yu Lai Wang, Mikako Sakurai, Jungkee Kwon, Mami Noda, Keiji Wada

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UCH-L3 belongs to the ubiquitin C-terminal hydrolase family that deubiquitinates ubiquitin-protein conjugates in the ubiquitin-proteasome system. A murine Uchl3 deletion mutant displays retinal degeneration, muscular degeneration, and mild growth retardation. To elucidate the function of UCH-L3, we investigated histopathological changes and expression of apoptosis- and oxidative stress-related proteins during retinal degeneration. In the normal retina, UCH-L3 was enriched in the photoreceptor inner segment that contains abundant mitochondria. Although the retina of Uchl3-deficient mice showed no significant morphological abnormalities during retinal development, prominent retinal degeneration became manifested after 3 weeks of age associated with photoreceptor cell apoptosis. Ultrastructurally, a decreased area of mitochondrial cristae and vacuolar changes were observed in the degenerated inner segment. Increased immunoreactivities for manganese superoxide dismutase, cytochrome c oxidase I, and apoptosis-inducing factor in the inner segment indicated mitochondrial oxidative stress. Expression of cytochrome c, caspase-1, and cleaved caspase-3 did not differ between wild-type and mutant mice; however, immunoreactivity for endonuclease G was found in the photoreceptor nuclei in the mutant retina. Hence, loss of UCH-L3 leads to mitochondrial oxidative stress-related photoreceptor cell apoptosis in a caspase-independent manner. Thus, Uchl3 -deficient mice represent a model for adult-onset retinal degeneration associated with mitochondrial impairment.

Original languageEnglish
Pages (from-to)132-141
Number of pages10
JournalAmerican Journal of Pathology
Issue number1
Publication statusPublished - Jul 2006


All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Sano, Y., Furuta, A., Setsuie, R., Kikuchi, H., Wang, Y. L., Sakurai, M., ... Wada, K. (2006). Photoreceptor cell apoptosis in the retinal degeneration of Uchl3-deficient mice. American Journal of Pathology, 169(1), 132-141.