Glutamate is effective in decreasing opacity formed in galactose-induced cataract model.

Although cataract is the leading cause of blindness worldwide, the detailed pathogenesis of cataract remains unclear, and clinically useful drug treatments are still lacking. In this study, we examined the effects of glutamate using an ex vivo model in which rat lens is cultured in a galactose-containing medium to induce opacity formation. After inducing lens opacity formation in galactose medium, glutamate was added, and the opacity decreased when the culture was continued. Next, microarray analysis was performed using samples in which the opacity was reduced by glutamate, and genes whose expression increased with galactose culture and decreased with the addition of glutamate were extracted. Subsequently, STRING analysis was performed on a group of genes that showed variation as a result of quantitative measurement of gene expression by RT-qPCR. The results suggest that apoptosis, oxidative stress, endoplasmic reticulum (ER) stress, cell proliferation, epithelial-mesenchymal transition (EMT), cytoskeleton, and histones are involved in the formation and reduction of opacity. Therefore, glutamate may reduce opacity by inhibiting oxidative stress and its downstream functions, and by regulating the cytoskeleton and cell proliferation.

Histone acetyltransferase inhibition reverses opacity in rat galactose-induced cataract.

Cataract, a disease that causes opacity of the lens, is the leading cause of blindness worldwide. Cataracts secondary to diabetes are common, even in young patients, so they are of significant clinical importance. Here, we used an ex vivo model of galactose-induced cataracts in the rat lens to investigate the therapeutic effects of histone acetyltransferase (HAT) inhibitors. Among the tested HAT inhibitors, TH1834 was the only one that could reverse most of the opacity once it had formed in the lens. Combination treatment with C646/CPTH2 and CBP30/CPTH2 also had therapeutic effects. In lens cross-sections, vacuoles were present in the tissue of the cortical equatorial region of untreated cataract samples. In treated cataract samples, lens tissue regenerated to fill the vacuoles. To identify the genes regulated by HAT inhibitors, qRT-PCR was performed on treated and untreated cataract samples to determine candidate genes. Expression of Acta1 and Stmn4, both of which are involved in the cytoskeleton, were altered significantly in C646+CPTH2 samples. Expression of Emd, a nuclear membrane protein, and Prtfdc1, which is involved in cancer cell proliferation, were altered significantly in CBP30+CPTH2 samples. Acta1, Acta2, Arrdc3, Hebp2, Hist2h2ab, Pmf1, Ppdpf, Rbm3, RGD1561694, Slc16a6, Slfn13, Tagln, Tgfb1i1, and Tuba1c in TH1834 samples were significantly altered. These genes were primarily related to regulation of cell proliferation, the cytoskeleton, and cell differentiation. Expression levels increased with the onset of cataracts and was suppressed in samples treated with HAT inhibitors.