Purchase this article with an account.
A.J. German Moring, J.M. Nickerson, J.H. Boatright; Protective Effects of Tauroursodeoxycholic Acid Against Oxidative Damage in Human Retinoblastoma Cells . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4551.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Animal and cell culture models of human retinitis pigmentosa (RP) suggest that apoptosis underlie part of the etiology of this disease family. Tauroursodeoxycholic acid (TUDCA) is an endogenous bile acid that reduces neuronal cytotoxicity in animal models of Huntington's disease and in drug-induced neuronal apoptosis both in cell culture and in vivo. The goal of the project was to investigate whether TUDCA inhibits apoptosis in human retinoblastoma cells undergoing oxidative damage. Tert-butyl hydroperoxide (tBH), a relatively stable chemical oxidant used extensively for studies of oxidative injury, was used to induce apoptosis. Methods: Human Y79 retinoblastoma cells were plated at a density of 2 x 106cells/ml. Cells were pretreated with 100 uM TUDCA for 30 minutes, followed by treatment with 200 uM tBH. Cells were pretreated with 100 uM TUDCA for 30 minutes, followed by treatment with increasing concentrations of tBH. After the treatment period, cells were mounted and cell damage and cell death patterns were visualized using in situ staining for DNA fragmentation (modified TUNEL). Cell counts from three areas of similar density were averaged for each sample and ANOVAs were performed with Neuman-Keuls post hoc tests. Results: Exposure to tBH resulted in a greater than three-fold increase in apoptotic cells. The number of apoptotic cells increased with increasing concentrations of tBH. Pretreatment with TUDCA significantly decreased apoptotic cell numbers. Control cells treated with TUDCA did not differ from entirely untreated cells (p < 0.01). Control cells treated with TUDCA did not differ from entirely untreated cells. Conclusions: Treatment with tBH induces apoptosis in human retinoblastoma cells. Pretreatment for a short period with TUDCA protects these cells from this oxidative injury. TUDCA is a nontoxic, endogenously produced bile acid that can be delivered systemically yet reaches CNS structures at therapeutic levels. The potential exists for TUDCA to delay or prevent retinal degenerations in millions of patients whose vision loss is currently untreatable. These data indicate that the potential therapeutic effects of TUDCA on retinal apoptosis and degeneration in animal and cell culture models of RP warrant further study.
This PDF is available to Subscribers Only