Mechanistical retinal drug targets and challenges

Rodríguez-Muela, 2012, Axonal damage, autophagy and neuronal survival, Autophagy, 8, 286, 10.4161/auto.8.2.18982 Strauss, 2005, The retinal pigment epithelium in visual function, Physiol. Rev., 85, 845, 10.1152/physrev.00021.2004 Palczewski, 2010, Retinoids for treatment of retinal diseases, Trends Pharmacol. Sci., 31, 284, 10.1016/j.tips.2010.03.001 Kim, 2013, Noncanonical autophagy promotes the visual cycle, Cell, 154, 365, 10.1016/j.cell.2013.06.012 Kaarniranta, 2013, Autophagy and heterophagy dysregulation leads to retinal pigment epithelium dysfunction and development of age-related macular degeneration, Autophagy, 9, 973, 10.4161/auto.24546 Guha, 2014, Rescue of compromised lysosomes enhances degradation of photoreceptor outer segments and reduces lipofuscin-like autofluorescence in retinal pigmented epithelial cells, Adv. Exp. Med. Biol., 801, 105, 10.1007/978-1-4614-3209-8_14 Valapala, 2014, Lysosomal-mediated waste clearance in retinal pigment epithelial cells is regulated by CRYBA1/βA3/A1-crystallin via V-ATPase-MTORC1 signaling, Autophagy, 10, 480, 10.4161/auto.27292 Sinha, 2016, Lysosomes: regulators of autophagy in the retinal pigmented epithelium, Exp. Eye Res., 144, 46, 10.1016/j.exer.2015.08.018 Caberoy, 2010, Tubby and tubby-like protein 1 are new MerTK ligands for phagocytosis, EMBO J., 29, 3898, 10.1038/emboj.2010.265 Kevany, 2010, Phagocytosis of retinal rod and cone photoreceptors, Physiology (Bethesda), 25, 8 Finnemann, 1997, Phagocytosis of rod outer segments by retinal pigment epithelial cells requires α(v)β5 integrin for binding but not for internalization, Proc. Natl. Acad. Sci. U. S. A., 94, 12932, 10.1073/pnas.94.24.12932 Nandrot, 2004, Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking alphavbeta5 integrin, J. Exp. Med., 200, 1539, 10.1084/jem.20041447 D'Cruz, 2000, Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat, Hum. Mol. Genet., 9, 645, 10.1093/hmg/9.4.645 Gal, 2000, Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa, Nat. Genet., 26, 270, 10.1038/81555 Feng, 2002, Mertk triggers uptake of photoreceptor outer segments during phagocytosis by cultured retinal pigment epithelial cells, J. Biol. Chem., 277, 17016, 10.1074/jbc.M107876200 Finnemann, 2003, Focal adhesion kinase signaling promotes phagocytosis of integrin-bound photoreceptors, EMBO J., 22, 4143, 10.1093/emboj/cdg416 Nandrot, 2007, Essential role for MFG-E8 as ligand for alphavbeta5 integrin in diurnal retinal phagocytosis, Proc. Natl. Acad. Sci. U. S. A., 104, 12005, 10.1073/pnas.0704756104 Vives-Bauza, 2008, The age lipid A2E and mitochondrial dysfunction synergistically impair phagocytosis by retinal pigment epithelial cells, J. Biol. Chem., 283, 24770, 10.1074/jbc.M800706200 Bavik, 2015, Visual cycle modulation as an approach toward preservation of retinal integrity, PLoS One, 10, 10.1371/journal.pone.0124940 Kiser, 2017, Rational tuning of visual cycle modulator pharmacodynamics, J. Pharmacol. Exp. Ther., 362, 131, 10.1124/jpet.117.240721 Kaarniranta, 2017, Autophagy regulates death of retinal pigment epithelium cells in age-related macular degeneration, Cell Biol. Toxicol., 33, 113, 10.1007/s10565-016-9371-8 Ferrington, 2016, Defects in retinal pigment epithelial cell proteolysis and the pathology associated with age-related macular degeneration, Prog. Retin. Eye Res., 51, 69, 10.1016/j.preteyeres.2015.09.002 Subrizi, 2015, Oxidative stress protection by exogenous delivery of rhHsp70 chaperone to the retinal pigment epithelium (RPE), a possible therapeutic strategy against RPE degeneration, Pharm. Res., 32, 211, 10.1007/s11095-014-1456-6 Viiri, 2013, Autophagy activation clears ELAVL1/HuR-mediated accumulation of SQSTM1/p62 during proteasomal inhibition in human retinal pigment epithelial cells, PLoS One, 8, e69563, 10.1371/journal.pone.0069563 Johansson, 2015, The marine n-3 PUFA DHA evokes cytoprotection against oxidative stress and protein misfolding by inducing autophagy and NFE2L2 in human retinal pigment epithelial cells, Autophagy, 11, 1636, 10.1080/15548627.2015.1061170 Mitter, 2014, Dysregulated autophagy in the RPE is associated with increased susceptibility to oxidative stress and AMD, Autophagy, 10, 1989, 10.4161/auto.36184 Russo, 2015, Autophagy dysregulation and the fate of retinal ganglion cells in glaucomatous optic neuropathy, Prog. Brain Res., 220, 87, 10.1016/bs.pbr.2015.04.009 Yao, 2016, Autophagy-mediated catabolism of visual transduction proteins prevents retinal degeneration, Autophagy, 12, 2439, 10.1080/15548627.2016.1238553 Kaarniranta, 2017, The Nobel prized cellular target autophagy in eye diseases, Acta Ophthalmol., 95, 335, 10.1111/aos.13344 Galluzzi, 2017, Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles, Nat. Rev. Drug Discov., 16, 487, 10.1038/nrd.2017.22 Boya, 2016, Autophagy in the eye: development, degeneration, and aging, Prog. Retin. Eye Res., 55, 206, 10.1016/j.preteyeres.2016.08.001 Kitaoka, 2013, Axonal protection by Nmnat3 overexpression with involvement of autophagy in optic nerve degeneration, Cell Death Dis., 17, 4:e860 Kaarniranta, 2012, Autophagy regulating kinases as potential therapeutic targets for age-related macular degeneration, Future Med. Chem., 4, 2153, 10.4155/fmc.12.169 Cheng, 2013, Therapeutic targeting of autophagy in disease: biology and pharmacology, Pharmacol. Rev., 65, 1162, 10.1124/pr.112.007120 Piippo, 2014, Decline in cellular clearance systems induces inflammasome signaling in human ARPE-19 cells, Biochim. Biophys. Acta, 1843, 3038, 10.1016/j.bbamcr.2014.09.015 Liu, 2016, Impairing autophagy in retinal pigment epithelium leads to inflammasome activation and enhanced macrophage-mediated angiogenesis, Sci. Rep., 6, 20639, 10.1038/srep20639 Kaarniranta, 2009, Heat shock proteins as gatekeepers of proteolytic pathways-implications for age-related macular degeneration (AMD), Ageing Res. Rev., 8, 128, 10.1016/j.arr.2009.01.001 Boulton, 1993, Lipofuscin is a photoinducible free radical generator, J. Photochem. Photobiol. B, 19, 201, 10.1016/1011-1344(93)87085-2 Terman, 2004, Lipofuscin, Int. J. Biochem. Cell Biol., 36, 1400, 10.1016/j.biocel.2003.08.009 Sparrow, 2003, A2E, a fluorophore of RPE lipofuscin: can it cause RPE degeneration?, Adv. Exp. Med. Biol., 533, 205, 10.1007/978-1-4615-0067-4_26 Nordgaard, 2008, Mitochondrial proteomics of the retinal pigment epithelium at progressive stages of age-related macular degeneration, Invest. Ophthalmol. Vis. Sci., 49, 2848, 10.1167/iovs.07-1352 Feng, 2014, Expression of endoplasmic reticulum stress markers GRP78 and CHOP induced by oxidative stress in blue light-mediated damage of A2E-containing retinal pigment epithelium cells, Ophthalmic Res., 52, 224, 10.1159/000363387 Salminen, 2017, Regulation of longevity by FGF21: interaction between energy metabolism and stress responses, Ageing Res. Rev., 37, 79, 10.1016/j.arr.2017.05.004 Minasyan, 2017, Protective mechanisms of the mitochondrial-derived peptide humanin in oxidative and endoplasmic reticulum stress in RPE cells, Oxidative Med. Cell. Longev., 2017, 1675230, 10.1155/2017/1675230 Hamasaki, 2013, Autophagosomes form at ER-mitochondria contact sites, Nature, 495, 389, 10.1038/nature11910 Matsunaga, 2016, Humanin protects RPE cells from endoplasmic reticulum stress-induced apoptosis by upregulation of mitochondrial glutathione, PLoS One, 11, 10.1371/journal.pone.0165150 Sreekumar, 2016, The mitochondrial-derived peptide humanin protects RPE cells from oxidative stress, senescence, and mitochondrial dysfunction, Invest. Ophthalmol. Vis. Sci., 57, 1238, 10.1167/iovs.15-17053 Xu, 2003, Requirements for passage of T lymphocytes across non-inflamed retinal microvessels, J. Neuroimmunol., 142, 47, 10.1016/S0165-5728(03)00258-3 Chen, 2015, Parainflammation, chronic inflammation, and age-related macular degeneration, J. Leukoc. Biol., 98, 713, 10.1189/jlb.3RI0615-239R Karlstetter, 2015, Retinal microglia: just bystander or target for therapy?, Prog. Retin. Eye Res., 45, 2030, 10.1016/j.preteyeres.2014.11.004 Langmann, 2007, Microglia activation in retinal degeneration, J. Leukoc. Biol., 81, 1345, 10.1189/jlb.0207114 Jack, 2005, TLR signaling tailors innate immune responses in human microglia and astrocytes, J. Immunol., 175, 4320, 10.4049/jimmunol.175.7.4320 Balak, 2017, IMO-8400, a toll-like receptor 7, 8, and 9 antagonist, demonstrates clinical activity in a phase 2a, randomized, placebo-controlled trial in patients with moderate-to-severe plaque psoriasis, Clin. Immunol., 174, 63, 10.1016/j.clim.2016.09.015 Cherry, 2014, Neuroinflammation and M2 microglia: the good, the bad, and the inflamed, J. Neuroinflammation, 11, 98, 10.1186/1742-2094-11-98 Shealy, 2008, Anti-TNF antibodies: lessons from the past, roadmap for the future, Handb. Exp. Pharmacol., 181, 101, 10.1007/978-3-540-73259-4_5 Zipfel, 2009, C, complement regulators and inhibitory proteins, Nat. Rev. Immunol., 9, 729, 10.1038/nri2620 Lakkaraju, 2014, Should I stay or should I go? Trafficking of sub-lytic MAC in the retinal pigment epithelium, Adv. Exp. Med. Biol., 801, 267, 10.1007/978-1-4614-3209-8_34 Lueck, 2011, Sub-lytic C5b-9 induces functional changes in retinal pigment epithelial cells consistent with age-related macular degeneration, Eye (Lond.), 25, 1074, 10.1038/eye.2011.109 Anderson, 2010, The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited, Prog. Retin. Eye Res., 29, 95, 10.1016/j.preteyeres.2009.11.003 Luo, 2011, Complement gene expression and regulation in mouse retina and retinal pigment epithelium/choroid, Mol. Vis., 17, 1588 Xu, 2016, Targeting the complement system for the management of retinal inflammatory and degenerative diseases, Eur. J. Pharmacol., 787, 94, 10.1016/j.ejphar.2016.03.001 Chen, 2007, Synthesis of complement factor H by retinal pigment epithelial cells is down-regulated by oxidized photoreceptor outer segments, Exp. Eye Res., 84, 635, 10.1016/j.exer.2006.11.015 Chen, 2008, Up-regulation of complement factor B in retinal pigment epithelial cells is accompanied by complement activation in the aged retina, Exp. Eye Res., 87, 543, 10.1016/j.exer.2008.09.005 Chen, 2010, Inhibition of the alternative pathway of complement activation reduces inflammation in experimental autoimmune uveoretinitis, Eur. J. Immunol., 40, 2870, 10.1002/eji.201040323 Vanaja, 2015, Mechanisms of inflammasome activation: recent advances and novel insights, Trends Cell Biol., 25, 308, 10.1016/j.tcb.2014.12.009 Sharma, 2016, The cell biology of inflammasomes: mechanisms of inflammasome activation and regulation, J. Cell Biol., 213, 617, 10.1083/jcb.201602089 Kauppinen, 2012, Oxidative stress activates NLRP3 inflammasomes in ARPE-19 cells-implications for age-related macular degeneration (AMD), Immunol. Lett., 147, 29, 10.1016/j.imlet.2012.05.005 Tseng, 2013, NLRP3 inflammasome activation in retinal pigment epithelial cells by lysosomal destabilization: implications for age-related macular degeneration, Invest. Ophthalmol. Vis. Sci., 54, 110, 10.1167/iovs.12-10655 Cassel, 2009, The NLRP3 inflammasome: a sensor of immune danger signals, Semin. Immunol., 21, 194, 10.1016/j.smim.2009.05.002 Shimada, 2012, Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis, Immunity, 36, 401, 10.1016/j.immuni.2012.01.009 Zhou, 2011, A role for mitochondria in NLRP3 inflammasome activation, Nature, 469, 221, 10.1038/nature09663 Triantafilou, 2013, The complement membrane attack complex triggers intracellular Ca2+ fluxes leading to NLRP3 inflammasome activation, J. Cell Sci., 126, 2903, 10.1242/jcs.124388 Tarallo, 2012, DICER1 loss and alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88, Cell, 149, 847, 10.1016/j.cell.2012.03.036 Chen, 2017, Activation of the TXNIP/NLRP3 inflammasome pathway contributes to inflammation in diabetic retinopathy: a novel inhibitory effect of minocycline, Inflamm. Res., 66, 157, 10.1007/s00011-016-1002-6 Jiang, 2001, IL-18 not required for IRBP peptide-induced EAU: studies in gene-deficient mice, Invest. Ophthalmol. Vis. Sci., 42, 177 Shen, 2014, Interleukin-18 has antipermeablity and antiangiogenic activities in the eye: reciprocal suppression with VEGF, J. Cell. Physiol., 229, 974, 10.1002/jcp.24575 Doyle, 2012, NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components, Nat. Med., 18, 791, 10.1038/nm.2717 Doyle, 2014, IL-18 attenuates experimental choroidal neovascularization as a potential therapy for wet age-related macular degeneration, Sci. Transl. Med., 6, 230ra44, 10.1126/scitranslmed.3007616 Ozaki, 2015, Targeting the NLRP3 inflammasome in chronic inflammatory diseases: current perspectives, J. Inflamm. Res., 8, 15