Treatment for Age-related Macular Degeneration
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Necessity
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Conciseness
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[1]Haijiang Lin, Bo Tian, Ahmad Al Moujahed, Joan W Miller, Demetrios G. Vavvas; Accumulation of damaged nDNA promotes RPE cellular senescence and pro-inflammation. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5235.
Creative contributions
Promising new treatments for AMD
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Using Senolytics to Treat AMD
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Retinal Pigment Epithelium Replacement Therapy
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Can we find some treatment cues from the complement system?
[1]Laufer J, Katz Y, Passwell JH . Extrahepatic synthesis of complement proteins in inflammation. Mol Immunol 2001
[2]Anderson DH, Mullins RF, Hageman GS, Johnson LV . A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol 2002; 134 (3): 411–431.
[3]Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C et al. Complement factor H polymorphism in age-related macular degeneration. Science 2005; 308 (5720): 385–389.
[4]Mullins RF, Schoo DP, Sohn EH, Flamme-Wiese MJ, Workamelahu G, Johnston RM, et al. The membrane attack complex in aging human choriocapillaris: relationship to macular degeneration and choroidal thinning. Am J Pathol. (2014) 184:3142–53. doi: 10.1016/j.ajpath.2014.07.017
[5]Mullins RF, Aptsiauri N, Hageman GS . Structure and composition of drusen associated with glomerulonephritis: implications for the role of complement activation in drusen biogenesis. Eye 2001; 15 (Part 3): 390–395.
[6]Leung E, Landa G. Update on current and future novel therapies for dry age-related macular degeneration. Expert Rev Clin Pharmacol. 2013;6(5):565–579. doi:10.1586/17512433.2013.829645
[7]http://apellis.com/pdfs/Press%20Release%20FILLY%2012%20Month%20Results%20FINAL%20FINAL%20170823.pdf.
[8]Yehoshua Z, Filho CADAG, Nunes RP, et al. Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study. Ophthalmology. 2014;121(3):693–701. doi:10.1016/j.ophtha.2013.09.044
[9]Mullins RF, Warwick AN, Sohn EH, Lotery AJ. From compliment to insult: genetics of the complement system in physiology and disease in the human retina. Hum Mol Genet. 2017;26(R1):R51–R57. doi:10.1093/hmg/ddx181
[10] Ricklin D, Mastellos DC, Reis ES, Lambris JD. The renaissance of complement therapeutics. Nat Rev Nephrol. 2018;14(1):26–47. doi:10.1038/nrneph.2017.156
[11]ClinicalTrials.gov. ZIMURA in combination with LUCENTIS in patients with Neovascular Age Related Macular Degeneration (NVAMD). 2017. NLM identifier: NCT03362190.
[12]Loyet KM, Good J, Davancaze T, et al. Complement inhibition in cynomolgus monkeys by anti-factor D antigen-binding fragment for the treatment of an advanced form of dry age-related macular degeneration. J Pharmacol Exp Ther. 2014;351(3):527–537. doi:10.1124/jpet.114.215921
[13]Volz C, Pauly D. Antibody therapies and their challenges in the treatment of age-related macular degeneration. Eur J Pharm Biopharm. 2015;95:158–172. doi:10.1016/j.ejpb.2015.02.020
[14]Wolf-Schnurrbusch UE, Stuck AK, Hess R, Wolf S, Enzmann V. Complement Factor P in choroidal neovascular membranes of patients with age-related macular degeneration. Retina. 2009;29(7):966–973. doi:10.1097/IAE.0b013e3181a2f40f
[15]Lesher A, Nilsson B, Song W-C. Properdin in complement activation and tissue injury. Mol Immunol. 2013;56(3):191–198. doi:10.1016/j.molimm.2013.06.002
[16]Bansal R. Method of inhibiting complement activation with factor Bb specific antibodies WO2009/029669A1. 2009.
[17]Safety and efficacy of IONIS-FB-Lrx in up to 120 patients 55 and older with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). NLM identifier: NCT03446144 Available from: https://clinicaltrials.gov/ct2/show/NCT03446144?term=IONIS-FB-Lrx&rank=2.
[18]Thurman JM, Kraus DM, Girardi G, et al. A novel inhibitor of the alternative complement pathway prevents antiphospholipid antibody-induced pregnancy loss in mice. Mol Immunol. 2005;42(1):87–97. doi:10.1016/j.molimm.2004.07.043
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PHOTO-COAGULATION & ANTIOXIDANT SUPPLEMENTATION
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Mitochondria Derived Peptides (MDPs) as potential treatment agents for AMD
[1]J. Blasiak, S. Glowacki, A. Kauppinen, and K. Kaarniranta, “Mitochondrial and nuclear DNA damage and repair in age-related macular degeneration,” International Journal of Molecular Sciences, vol. 14, no. 2, pp. 2996–3010, 2013.
[2]F. Q. Liang and B. F. Godley, “Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: a possible mechanism for RPE aging and age-related macular degeneration,” Experimental Eye Research, vol. 76, no. 4, pp. 397–403, 2003.
[3]Karunadharma, P.P.; Nordgaard, C.L.; Olsen, T.W.; Ferrington, D.A. Mitochondrial DNA. Damage as a potential mechanism for age-related macular degeneration. Invest Ophthalmol Vis. Sci. 2010, 51, 5470–5479.
[4]Fuku, N.; Pareja-Galeano, H.; Zempo, H.; Alis, R.; Arai, Y.; Lucia, A.; Hirose, N. The mitochondrial-derived peptide MOTS-c: A player in exceptional longevity? Aging Cell 2015, 14, 921–923.
[5]Hashimoto Y., Niikura T., Tajima H., Yasukawa T., Sudo H., Ito Y., Kita Y., Kawasumi M., Kouyama K., Doyu M., et al. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer’s disease genes and Abeta. Proc. Natl. Acad. Sci. USA. 2001;98:6336–6341. doi:10.1073/pnas.101133498
[6]P. G. Sreekumar, K. Ishikawa, C. Spee et al., “The mitochondrial-derived peptide humanin protects RPE cells from oxidative stress, senescence, and mitochondrial dysfunction,” Investigative Ophthalmology & Visual Science, 2016, vol. 57, no. 3, pp. 1238–1253, 2016.
[7]Y. Hashimoto, T. Niikura, Y. Ito et al., “Detailed characterization of neuroprotection by a rescue factor humanin against various Alzheimer’s disease-relevant insults,” Journal of Neuroscience, vol. 21, no. 23, pp. 9235–9245, 2001.
[8]Y. Hashimoto, H. Suzuki, S. Aiso, T. Niikura, I. Nishimoto, and M. Matsuoka, “Involvement of tyrosine kinases and STAT3 in Humanin-mediated neuroprotection,” Life Sciences, vol. 77, no. 24, pp. 3092–3104, 2005.
[9] S. J. Kim, N. Guerrero, G. Wassef et al., “The mitochondrial-derived peptide humanin activates the ERK1/2, AKT, and STAT3 signaling pathways and has age-dependent signaling pathways and has age-dependent signaling differences in the hippocampus,” Oncotarget, vol. 7, no. 30, pp. 46899–46912, 2016.
[10]Yang L., Tan Z., Wang D., Xue L., Guan M.X., Huang T., Li R. Species identification through mitochondrial rRNA genetic analysis. Sci. Rep. 2014;4:4089. doi: 10.1038/srep04089.
[11]Nashine S., Cohen P., Nesburn A.B., Kuppermann B.D., Kenney M.C. Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration. Sci. Rep. 2018;8:15175. doi: 10.1038/s41598-018-33290-5.