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A. J. Chucair, S. Chollangi, N. P. Rotstein, L. E. Politi, J. D. Ash; Lif Protects Photoreceptors From Induced Oxidative Stress in Pure Primary Neuronal Cultures of Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2069.
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© ARVO (1962-2015); The Authors (2016-present)
Activation of the gp130 receptor by Leukemia inhibitory factor (LIF) prevents photoreceptor cell death in vivo, but has the unwanted side effect of reducing function of retinal neurons. Developing a culture model in which LIF can protect cells from oxidative injury would facilitate identification of the molecular mechanism of protection. The purpose of this study was to define a primary cell culture model in which LIF protects photoreceptors from oxidative damage in a dose and receptor dependent mechanism.
We have previously developed a primary culture model of purified rat retinal neurons grown in defined medium, in which amacrine neurons and photoreceptors are the two major cell types. Neurons obtained from newborn rat retinas were cultured in defined medium alone or supplemented with different concentrations of LIF at day 0. At day 3, cells were treated with the oxidant paraquat (PQ) for 24 hours. Opsin expression, cell death and nuclear fragmentation were evaluated to determine the effects of LIF on photoreceptor differentiation and survival.
After PQ treatment, cultures without LIF had a significantly higher rate of photoreceptor death than cultures treated with LIF. As expected from previous studies LIF also reduced opsin expression in our culture model. In the culture model, inhibition of opsin expression required lower concentrations of LIF while photoreceptor protection required higher concentrations.
Our results show that LIF can protect photoreceptors from PQ-induced oxidative stress in pure retina neuronal cultures in the absence of growing Muller glial cells and demonstrate that photoreceptors in culture respond directly to LIF and protection is not an indirect consequence of Muller cell stimulation. We propose this neuronal culture system as a suitable model to determine the mechanisms involved in neuroprotection against oxidative stress. Since LIF also reduced opsin expression, this model will be useful to determine if neuroprotection and reduced phototransduction gene expression are regulated by independent molecular mechanisms.
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