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John D Ash, Huiming Xia, Yingxiang Huang, Lei Xu, Ping Zhu, Ana J Chucair-Elliott; Leukemia Inhibitory Factor (LIF) induces survival of Retinal Pigment Epithelium. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5752.
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Retinal Pigment Epithelium (RPE) dysfunction and degeneration is associated with vision loss in age-related macular degeneration (AMD), geographic atrophy, serous retinal detachment, and other diseases. The purpose of this study was to determine whether leukemia inhibitory factor (LIF) could protect RPE from cell death and preserve vision.
A 2ul solution of LIF (1.6 mg/ml) was injected into vitreous space of Balbc/J mice to induce protective responses. PBS was injected into the contralateral eye as a control. Two days after injection, mice were given a single intraperitoneal injection of sodium iodate in a range of concentrations from 0 to 50mg/kg We also injected sodium iodate into mice lacking STAT3 in RPE. Structural and functional integrity of RPE was examined by Electroretinogram (ERG) c-wave recordings, Optical coherence tomography (OCT) imaging, and histology. Eyes were enucleated and either RPE choroid flatmounts or frozen sections were stained with phalloidin to label filamentous actin or antibodies to ZO-1 or RPE65.
Sodium Iodate treatment dramatically reduced c-wave response in a dose dependent manner in PBS injected or uninjected eyes. Severe damage was observed in mice given doses of 25 mg/kg body weight sodium iodate or higher. Pretreating eyes with LIF increased the threshold of significant c-wave loss to 40 mg/kg. OCT imaging demonstrated that in PBS treated eyes, sodium iodate induced loss of RPE followed by serous retinal detachment. LIF injected eyes were normal at the same dose of sodium iodate. Immuno- and histological staining of RPE demonstrated that LIF injected eyes had significantly smaller areas of RPE damage than PBS injected eyes. Mice lacking STAT3 demonstrated increased RPE degeneration in response to sodium iodate treatment.
Our data demonstrate that LIF mediated STAT3 activation in RPE can significantly increase the damage threshold of RPE to injury induced by sodium iodate. LIF expression is induced in the eye in response to oxidative stress, and our data suggests that LIF is an important survival factor for RPE cells. This suggests a therapeutic potential for LIF in degenerations involving death of the RPE.
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