E potential impact of new treatments. Arch Ophthalmol. 2009;127(4):533?0. doi:10.1001/archophthalmol.2009.58. 52. Cherry AB, Daley GQ. Reprogramming cellular identity for regenerative medicine. Cell. 2012;148(6):1110?2. doi:10.1016/j. cell.2012.02.031. 53. Bar-Nur O, Russ HA, Efrat S, Benvenisty N. Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. Cell Stem Cell. 2011;9(1):17?3. doi:10.1016/j.stem.2011.06.007. 54. Hu Q, Friedrich AM, Johnson LV, Clegg DO. Memory in induced pluripotent stem cells: reprogrammed human Nectrolide web retinal-pigmented epithelial cells show tendency for spontaneous redifferentiation. Stem Cells. 2010;28(11):1981?1. doi:10.1002/stem.531. 55. Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, et al. PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25679764 Epigenetic memory in induced pluripotent stem cells. Nature. 2010;467(7313):285?0. doi:10.1038/nature09342. 56. Sullivan GJ, Bai Y, Fletcher J, Wilmut I. Induced pluripotent stem cells: epigenetic memories and practical implications. Mol Hum Reprod. 2010;16(12):880?. doi:10.1093/molehr/gaq091. 57. Polo JM, Liu S, Figueroa ME, Kulalert W, Eminli S, Tan KY, et al. Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol. 2010;28(8):848?5. doi:10.1038/nbt.1667. 58. Rose S, Frye RE, Slattery J, Wynne R, Tippett M, Pavliv O, et al. Oxidative stress induces mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines in a well-matched case control cohort. Plos ONE. 2014;9(1):e85436. doi:10.1371/journal.pone.0085436. 59. Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell. 2012;48(2):158?7. doi:10.1016/j. molcel.2012.09.025. 60. Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science. 2003;300(5622):1140?. doi:10.1126/science.1082889. 61. AZD3759 biological activity Hardie DG, Ross FA, Hawley SA. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 2012;13(4):251?2. doi:10.1038/nrm3311. 62. Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011;13(2):132?1. doi:10.1038/ncb2152. 63. Wang AL, Lukas TJ, Yuan M, Du N, Tso MO, Neufeld AH. Autophagy and exosomes in the aged retinal pigment epithelium: possible relevance to drusen formation and age-related macular degeneration. PLoS ONE. 2009;4(1):e4160. doi:10.1371/journal.pone.0004160. 64. Field MG, Comer GM, Kawaji T, Petty HR, Elner VM. Noninvasive imaging of mitochondrial dysfunction in dry age-related macular degeneration. Ophthalmic Surg Lasers Imaging. 2012;43(5):358?5. doi:10.3928/15428877-20120712-02.Golestaneh et al. J Transl Med (2016) 14:Page 17 of65. Beatty S, Koh H, Phil M, Henson D, Boulton M. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol. 2000;45(2):115?4. 66. Liang H, Ward WF. PGC-1alpha: a key regulator of energy metabolism. Adv Physiol Educ. 2006;30(4):145?1. doi:10.1152/advan.00052.2006. 67. Saint-Geniez M, Jiang A, Abend S, Liu L, Sweigard H, Connor KM, et al. PGC-1alpha regulates normal and pathological angiogenesis in the retina. Am J Pathol. 2013;182(1):255?5. doi:10.1016/j.ajpath.2012.09.003.68. Jager S, Handschin C, St-Pierre J, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct.E potential impact of new treatments. Arch Ophthalmol. 2009;127(4):533?0. doi:10.1001/archophthalmol.2009.58. 52. Cherry AB, Daley GQ. Reprogramming cellular identity for regenerative medicine. Cell. 2012;148(6):1110?2. doi:10.1016/j. cell.2012.02.031. 53. Bar-Nur O, Russ HA, Efrat S, Benvenisty N. Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. Cell Stem Cell. 2011;9(1):17?3. doi:10.1016/j.stem.2011.06.007. 54. Hu Q, Friedrich AM, Johnson LV, Clegg DO. Memory in induced pluripotent stem cells: reprogrammed human retinal-pigmented epithelial cells show tendency for spontaneous redifferentiation. Stem Cells. 2010;28(11):1981?1. doi:10.1002/stem.531. 55. Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, et al. PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25679764 Epigenetic memory in induced pluripotent stem cells. Nature. 2010;467(7313):285?0. doi:10.1038/nature09342. 56. Sullivan GJ, Bai Y, Fletcher J, Wilmut I. Induced pluripotent stem cells: epigenetic memories and practical implications. Mol Hum Reprod. 2010;16(12):880?. doi:10.1093/molehr/gaq091. 57. Polo JM, Liu S, Figueroa ME, Kulalert W, Eminli S, Tan KY, et al. Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol. 2010;28(8):848?5. doi:10.1038/nbt.1667. 58. Rose S, Frye RE, Slattery J, Wynne R, Tippett M, Pavliv O, et al. Oxidative stress induces mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines in a well-matched case control cohort. Plos ONE. 2014;9(1):e85436. doi:10.1371/journal.pone.0085436. 59. Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell. 2012;48(2):158?7. doi:10.1016/j. molcel.2012.09.025. 60. Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science. 2003;300(5622):1140?. doi:10.1126/science.1082889. 61. Hardie DG, Ross FA, Hawley SA. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 2012;13(4):251?2. doi:10.1038/nrm3311. 62. Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011;13(2):132?1. doi:10.1038/ncb2152. 63. Wang AL, Lukas TJ, Yuan M, Du N, Tso MO, Neufeld AH. Autophagy and exosomes in the aged retinal pigment epithelium: possible relevance to drusen formation and age-related macular degeneration. PLoS ONE. 2009;4(1):e4160. doi:10.1371/journal.pone.0004160. 64. Field MG, Comer GM, Kawaji T, Petty HR, Elner VM. Noninvasive imaging of mitochondrial dysfunction in dry age-related macular degeneration. Ophthalmic Surg Lasers Imaging. 2012;43(5):358?5. doi:10.3928/15428877-20120712-02.Golestaneh et al. J Transl Med (2016) 14:Page 17 of65. Beatty S, Koh H, Phil M, Henson D, Boulton M. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol. 2000;45(2):115?4. 66. Liang H, Ward WF. PGC-1alpha: a key regulator of energy metabolism. Adv Physiol Educ. 2006;30(4):145?1. doi:10.1152/advan.00052.2006. 67. Saint-Geniez M, Jiang A, Abend S, Liu L, Sweigard H, Connor KM, et al. PGC-1alpha regulates normal and pathological angiogenesis in the retina. Am J Pathol. 2013;182(1):255?5. doi:10.1016/j.ajpath.2012.09.003.68. Jager S, Handschin C, St-Pierre J, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct.
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