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Jiangang Wang, Lei Xu, Jacquelynn Nguyen, Ratanmani Joshi, John D. Ash; Common Gene Expression Profiles Of Induced Neuroprotection By Preconditioning And By Injection Of Leukemia Inhibitory Factor. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5437.
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© ARVO (1962-2015); The Authors (2016-present)
We have shown that in the adult albino mouse, preconditioning with mild bright cyclic light or intravitreal injection of leukemia inhibitory factor (LIF) preserved photoreceptor function and prevented photoreceptor loss from an acute light damage. Both preconditioning and LIF injection have been shown to have broad-spectrum protective activity that requires STAT3 activation. The purpose of this study was to profile gene expression changes that are common between preconditioning and LIF injection to help identify the molecular mechanism of protection.
Adult albino mice are exposed to damaging light (4000 lux) for 4 hours following either 6-day cyclic bright light (800 lux) preconditioning or low dose LIF (0.25 ug) injection. Retinas were collected before and after light damage. Total RNA was extracted using Trizol (Invitrogen) and the RNA was purified using RNeasy kit (Qiagen). Gene expression profiling of the purified RNA samples was performed using the Illumina's MouseRef-8 v2.0 Expression BeadChip. Statistical analysis of the expression patterns was performed using GeneSpring GX 11. The "Ingenuity Pathway Analysis" software (IPA ingenuity systems) was used to elucidate putative pathways associated with the gene expression changes in the retinas. Real-time PCR was used to confirm expression changes.
Expression analyses show that induced protection whether by LIF or preconditioning induce similar but not identical patterns of gene expression changes. Common functional groups regulated by preconditioning and LIF include: Immune response genes (host defense, immune cell trafficking, and antigen presentation), DNA repair, retinoid cycle genes, cell cycle, anti-apoptosis, and mitochondrial function genes.
We have compared the common gene expression changes in our two data sets since these are likely to include the mechanism of protection that is downstream of STAT3. The results suggest that cytokine induced broad spectrum protection is the result of multiple protective pathways being activated. This could explain how a single cytokine can induce protection from genetic mutations, oxidative stress, ER stress, or mechanical injury.
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