| First Author | Ando R | Year | 2014 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 55 |
| Issue | 7 | Pages | 4682-90 |
| PubMed ID | 24994871 | Mgi Jnum | J:230151 |
| Mgi Id | MGI:5755569 | Doi | 10.1167/iovs.13-13272 |
| Citation | Ando R, et al. (2014) Decreased proteasomal activity causes photoreceptor degeneration in mice. Invest Ophthalmol Vis Sci 55(7):4682-90 |
| abstractText | PURPOSE: To study the retinal degeneration caused by decreased proteasomal activity in beta5t transgenic (beta5t-Tg) mice, an animal model of senescence acceleration. METHODS: beta5t-Tg mice and age-matched littermate control (WT) mice were used. Proteasomal activities and protein level of poly-ubiquitinated protein in retinal extracts were quantified. Fundus images of beta5t-Tg mice were taken and their features were assessed. For histologic evaluation, the thicknesses of inner nuclear layer (INL), outer nuclear layer (ONL), and photoreceptor outer segment (OS) were measured. For functional analysis, ERG was recorded under scotopic and photopic illumination conditions. Immunofluorescence (IF) staining and TUNEL were performed to investigate the mechanism of photoreceptor degeneration. RESULTS: Chymotrypsin-like activity was partially suppressed in retinal tissues of beta5t-Tg mice. Retinal degenerative changes with arterial attenuation were present in beta5t-Tg, but not in WT mice. Inner nuclear layer thickness showed no significant change between beta5t-Tg and WT mice at 1, 3, 6, and 9 months of age. By contrast, thicknesses of ONL and OS in beta5t-Tg mice were significantly decreased at 3, 6, and 9 months compared with those in WT mice. Electroretinograms showed decrease of scotopic a-wave amplitude in beta5t-Tg mice. The number of TUNEL-positive cells in ONL were significantly increased in beta5t-Tg mice and colocalized with apoptosis-inducing factor, but not with cleaved caspase-3 and -9, indicating that the photoreceptor cell death was induced via a caspase-independent pathway. CONCLUSIONS: The current data showed that impaired proteasomal function causes photoreceptor degeneration. |
