LIF expression is induced in M?ller cells in response to photoreceptor stress caused by inherited mutations. Inhibiting the LIF receptor with antagonists, or knocking out the co-receptor gp130, or the signaling target STAT3 in photoreceptors, accelerates degeneration. These results show that induced LIF delays the onset and rate of retinal degeneration. We have also shown that expression of LIF decreases significantly during the time of rapid photoreceptor degeneration, and our published studies show that we can dramatically delay inherited degeneration by keeping LIF levels elevated. These results show that progression of disease is regulated by expression of LIF in M?ller cells. Understanding both the induction of LIF early in disease and its suppressed expression later in disease is necessary to understand one mechanism that can determine the age of onset and rate of retinal degeneration. Understanding the regulation of LIF would also lead to the identification of potential targets that can be manipulated to promote neuronal survival by inducing and maintaining LIF expression. The goal of this project is to determine both the mechanism for induced LIF expression and the mechanism for reduction of expression that coincides with rapid degeneration. The proposal will determine the role of three receptor-signaling pathways that can coordinate to either induce or maintain LIF expression, and will determine the role to the LIF cis-acting elements in suppressing LIF expression

National Institute of Health (NIH)
National Eye Institute (NEI)
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Neuhold, Lisa
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University of Florida
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Brown, Emily E; Lewin, Alfred S; Ash, John D (2018) Mitochondria: Potential Targets for Protection in Age-Related Macular Degeneration. Adv Exp Med Biol 1074:11-17
Xu, Lei; Kong, Li; Wang, Jiangang et al. (2018) Stimulation of AMPK prevents degeneration of photoreceptors and the retinal pigment epithelium. Proc Natl Acad Sci U S A 115:10475-10480
Hooper, Marcus J; Wang, Jiangang; Browning, Robert et al. (2018) Damage-associated molecular pattern recognition is required for induction of retinal neuroprotective pathways in a sex-dependent manner. Sci Rep 8:9115
Hooper, Marcus J; Ash, John D (2018) Müller Cell Biological Processes Associated with Leukemia Inhibitory Factor Expression. Adv Exp Med Biol 1074:479-484
Abrahan, Carolina; Ash, John D (2016) Erratum to: The Potential Use of PGC-1? and PGC-1? to Protect the Retina by Stimulating Mitochondrial Repair. Adv Exp Med Biol 854:E1
Abrahan, Carolina; Ash, John D (2016) The Potential Use of PGC-1? and PGC-1? to Protect the Retina by Stimulating Mitochondrial Repair. Adv Exp Med Biol 854:403-9
Xu, Lei; Ash, John D (2016) The Role of AMPK Pathway in Neuroprotection. Adv Exp Med Biol 854:425-30
Ildefonso, Cristhian J; Jaime, Henrique; Brown, Emily E et al. (2016) Targeting the Nrf2 Signaling Pathway in the Retina With a Gene-Delivered Secretable and Cell-Penetrating Peptide. Invest Ophthalmol Vis Sci 57:372-86
Reagan, Alaina; Gu, Xiaowu; Hauck, Stefanie M et al. (2016) Retinal Caveolin-1 Modulates Neuroprotective Signaling. Adv Exp Med Biol 854:411-8
Fu, Suhua; Zhu, Meili; Ash, John D et al. (2014) Investigating the role of retinal Müller cells with approaches in genetics and cell biology. Adv Exp Med Biol 801:401-5

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