| First Author | Wignes JA | Year | 2013 |
| Journal | Exp Eye Res | Volume | 115 |
| Pages | 263-73 | PubMed ID | 23872361 |
| Mgi Jnum | J:210399 | Mgi Id | MGI:5571003 |
| Doi | 10.1016/j.exer.2013.06.026 | Citation | Wignes JA, et al. (2013) p62 expression and autophagy in alphaB-crystallin R120G mutant knock-in mouse model of hereditary cataract. Exp Eye Res 115:263-73 |
| abstractText | The formation of cataracts is associated with the accumulation of protein aggregates in the ocular lens, suggesting that defective protein degradation plays a role in cataract pathogenesis. Accumulation of the p62 protein has recently been identified as a marker for impaired autophagy in a variety of tissues; however, little information exists on its expression in the ocular lens and in cataracts. In the present study we examined the expression of p62 in the mouse lens and compared its expression in wild-type lenses with that in lenses from knock-in mice with an arginine to glycine mutation in alphaB-crystallin (alphaB-R120G) that is known to cause human hereditary cataract. Immunohistochemical, immunoblotting, and transmission electron microscopic analyses of wild type and alphaB-R120G mutant mice were performed. To assess the effect of increased protein aggregation on autophagy, immunohistochemical staining was performed with an anti-p62 antibody, revealing the presence of p62-positive punctate staining in a band of denucleated cortical fiber cells. The number and size of p62 puncta were significantly greater in alphaB-R120G homozygous mutant lenses than in wild type and heterozygous mutant lenses. p62 staining was also abundant in lens epithelial cells and was concentrated around the nuclear membrane. Double-membraned structures similar to autophagosomes containing cellular cytoplasmic content were detected in lens epithelial cells by transmission electron microscopy. The autophagosomes in lens epithelial cells from alphaB-R120G homozygous mutant mice were larger than those in wild type mice. Double-membraned structures that are probably autophagosomes were also detected in cortical fiber cells and were more abundant in the alphaB-R120G homozygous mutant lens than the wild type lens. This study demonstrates p62 distribution as speckles in the lens fiber cells, altered levels of p62 expression, and the presence of autophagosomes in the ocular lens of alphaB-R120G mutant mice. We propose that autophagy is inhibited in the alphaB-R120G mutant lenses because of a defect in protein degradation after autophagosome formation. Further work is necessary to determine the relationship between alphaB-crystallin function, autophagy, and cataract formation. |
