Oxidative stress defense and repair systems of the ocular lens.
ABSTRACT It is well accepted that reactive oxygen species (ROS) play a critical role in many biological processes including disease and longevity. Oxidation of proteins has been linked to many disease states and even the aging process itself. This was first proposed as "The free radical theory of aging" in 1956 by Denham Harman which suggests that free radicals causes cumulative and irreversible damage to macromolecules, loss of cellular function and cell death over time directly impacting health and lifespan. Cellular damage from ROS exposure has been termed oxidative stress, which is an imbalance between cellular ROS production and the ability of the cell to regulate ROS levels and repair damage caused by ROS. This review focuses on the role of oxidative stress in the eye lens as a model for understanding the role of oxidative stress systems in age-related human disease.
- SourceAvailable from: Ales Cvekl[show abstract] [hide abstract]
ABSTRACT: Mutation of the autophagy gene FYVE (named after the four cysteine-rich proteins: Fab 1 [yeast orthologue of PIKfyve], YOTB, Vac 1 [vesicle transport protein], and EEA1) and coiled coil containing 1 (fyco1) causes human cataract suggesting a role for autophagy in lens function. Here, we analyzed the range and spatial expression patterns of lens autophagy genes and we evaluated whether autophagy could be induced in lens cells exposed to stress. Autophagy gene expression levels and their spatial distribution patterns were evaluated between microdissected human lens epithelium and fibers at the mRNA and protein levels by microarray data analysis, real-time PCR and western blot analysis. Selected autophagy protein spatial expression patterns were also examined in newborn mouse lenses by immunohistochemistry. The autophagosomal content of cultured human lens epithelial cells was determined by counting the number of microtubule-associated protein 1 light chain 3B (LC3B)-positive puncta in cells cultured in the presence or absence of serum. A total of 42 autophagy genes were detected as being expressed by human lens epithelium and fibers. The autophagosomal markers LC3B and FYCO1 were detected throughout the newborn mouse lens. Consistently, the autophagy active form of LC3B (LC3B II) was detected in microdissected human lens fibers. An increased number of LC3B-positive puncta was detected in cultured lens cells upon serum starvation suggesting induction of autophagy in lens cells under stress conditions. The data provide evidence that autophagy is an important component for the function of lens epithelial and fiber cells. The data are consistent with the notion that disruption of lens autophagy through mutation or inactivation of specific autophagy proteins could lead to loss of lens resistance to stress and/or loss of lens differentiation resulting in cataract formation.Molecular vision 01/2012; 18:1773-86. · 1.99 Impact Factor