Lens epithelial cell apoptosis appears to be a common cellular basis for non-congenital cataract development in humans and animals.

Abstract

Abstract. Cataract is a major ocular disease that causes blindness in many developing countries of the world. It is well established that various factors such as oxidative stress, UV, and other toxic agents can induce both in vivo and in vitro cataract formation. However, a common cellular basis for this induction has not been previously recognized. The present study of lens epithelial cell viability suggests such a general mechanism. When lens epithelial cells from a group of 20 cataract patients 12 to 94 years old were analyzed by terminal deoxynucleotidyl transferase (TdT) labeling and DNA fragmentation assays, it was found that all of these patients had apoptotic epithelial cells ranging from 4.4 to 41.8%. By contrast, in eight normal human lenses of comparable age, very few apoptotic epithelial cells were observed.We suggest that cataract patients may have deficient defense systems against factors such as oxidative stress and UV at the onset of the disease. Such stress can trigger lens epithelial cell apoptosis that then may initiate cataract development. To test this hypothesis, it is also demonstrated here that hydrogen peroxide at concentrations previously found in some cataract patients induces both lens epithelial cell apoptosis and cortical opacity. Moreover, the temporal and spatial distribution of induced apoptotic lens epithelial cells precedes development of lens opacification. These results suggest that lens epithelial cell apoptosis may be a common cellular basis for initiation of noncongenital cataract formation.

Human αA- and αB-crystallins bind to Bax and Bcl-XS to sequester their translocation during staurosporine-induced apoptosis

“…pEGFP-HLE, pEGFP-HaA-HLE and pEGFP-HaB-HLE cells were grown to 100% confluence, then treated with 100 nM staurosporine or 0.01% DMSO (control) for 6 h. Then, the cells were harvested for isolation of genomic DNA and the isolated DNA samples were analyzed with 2.0% agarose gel as described previously. 4 The 123 bp marker from Gibco BRL was shown on the left. STS: staurosporine HaA-and HaB-crystallins prevent staurosporineinduced upregulation of Bak in human lens epithelial cells…”

“…99 The apoptotic nature of the treated cells was further verified by DNA fragmentation and Hoechst staining as previously described. 4,44,45,99 Protein preparation and Western blotting analysis…”

“…[1][2][3] In lens system, our previous work [4][5][6] has suggested that induced lens epithelial cell apoptosis appears to be a common cellular mechanism mediating stress-induced, noncongenital cataractogenesis. Subsequently, several laboratories have reported that lens epithelial cell apoptosis is indeed actively involved in lens pathogenesis as demonstrated from in vivo animal model studies.…”

Downregulation of gene expression in the ageing lens: a possible contributory factor in senile cataract

“…Oxidative stress, ultraviolet radiation, and other toxic factors can induce the formation of cataract in vitro and in vivo. 1,11 The formation of senile cataract is a universal ageing process accompanied by numerous morphological and functional changes in the lens cells. This study was undertaken to investigate the molecular characteristic of lens epithelial cells from patients with senile cataract.…”

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“…Alternatively, HSPB1 might be involved in cataract, because HSPB1, CRYAA and CRYAB interact with each other and all can negatively regulate apoptotic process (Table 4). Studies suggested that lens epithelial cell apoptosis may be a common cellular basis for initiation of non-congenital cataract formation (Li et al 1995), and inhibition of epithelial cell apoptosis may be one possible mechanism that inhibits cataract development (Nahomi et al 2013). Our results here argue for further experimental studies to test the possible role of HSPB1 CNVs in cardiomyopathy or cataract/blindness in African Americans.…”