{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:49:26Z","timestamp":1790700566191,"version":"4.1.0"},"reference-count":164,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2017,6,2]],"date-time":"2017-06-02T00:00:00Z","timestamp":1496361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["TL1 TR001107"],"award-info":[{"award-number":["TL1 TR001107"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1 TR001108"],"award-info":[{"award-number":["UL1 TR001108"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Chinese University of Hong Kong","award":["2041771"],"award-info":[{"award-number":["2041771"]}]},{"name":"Research Grants Council of Hong Kong","award":["2140694"],"award-info":[{"award-number":["2140694"]}]},{"name":"National Scientific Foundation of China","award":["81486126"],"award-info":[{"award-number":["81486126"]}]},{"name":"Provincial Natural Scientific Foundation of China","award":["8151503102000019"],"award-info":[{"award-number":["8151503102000019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Zebrafish are a popular vertebrate model in drug discovery. They produce a large number of small and rapidly-developing embryos. These embryos display rich visual-behaviors that can be used to screen drugs for treating retinal degeneration (RD). RD comprises blinding diseases such as Retinitis Pigmentosa, which affects 1 in 4000 people. This disease has no definitive cure, emphasizing an urgency to identify new drugs. In this review, we will discuss advantages, challenges, and research developments in using zebrafish behaviors to screen drugs in vivo. We will specifically discuss a visual-motor response that can potentially expedite discovery of new RD drugs.<\/jats:p>","DOI":"10.3390\/ijms18061185","type":"journal-article","created":{"date-parts":[[2017,6,2]],"date-time":"2017-06-02T10:20:44Z","timestamp":1496398844000},"page":"1185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Utilizing Zebrafish Visual Behaviors in Drug Screening for Retinal Degeneration"],"prefix":"10.3390","volume":"18","author":[{"given":"Logan","family":"Ganzen","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Purdue University, 915 W. State Street, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prahatha","family":"Venkatraman","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Purdue University, 915 W. State Street, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuk","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Purdue University, 915 W. State Street, West Lafayette, IN 47907, USA"},{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine Lafayette, 625 Harrison Street, West Lafayette, IN 47907, USA"},{"name":"Purdue Institute for Integrative neuroscience, 610 Purdue Mall, Purdue University, West Lafayette, IN 47907, USA"},{"name":"Purdue Institute for Drug Discovery, 610 Purdue Mall, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Joint Shantou International Eye Center, Shantou University &amp; the Chinese University of Hong Kong, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/S0140-6736(06)69740-7","article-title":"Retinitis pigmentosa","volume":"368","author":"Hartong","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.preteyeres.2010.03.004","article-title":"The molecular basis of human retinal and vitreoretinal diseases","volume":"29","author":"Berger","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1750-1172-1-40","article-title":"Retinitis pigmentosa","volume":"1","author":"Hamel","year":"2006","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.preteyeres.2007.08.002","article-title":"Zebrafish: A model system for the study of eye genetics","volume":"27","author":"Fadool","year":"2008","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.jaapos.2009.10.004","article-title":"Leber congenital amaurosis: Clinical correlations with genotypes, gene therapy trials update, and future directions","volume":"13","author":"Chung","year":"2009","journal-title":"J. Am. Assoc. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_6","unstructured":"Weleber, R.G., Francis, P.J., Trzupek, K.M., and Beattie, C. (2017, January 26). Leber Congenital Amaurosis, Available online: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20301475."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/343364a0","article-title":"A point mutation of the rhodopsin gene in one form of retinitis pigmentosa","volume":"343","author":"Dryja","year":"1990","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9370","DOI":"10.1073\/pnas.88.20.9370","article-title":"Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa","volume":"88","author":"Dryja","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/ng0796-358","article-title":"Missense mutation in the gene encoding the \u03b1 subunit of rod transducin in the Nougaret form of congenital stationary night blindness","volume":"13","author":"Dryja","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.ajhg.2009.06.016","article-title":"Homozygosity mapping reveals PDE6C mutations in patients with early-onset cone photoreceptor disorders","volume":"85","author":"Thiadens","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"19581","DOI":"10.1073\/pnas.0907720106","article-title":"A homologous genetic basis of the murine cpfl1 mutant and human achromatopsia linked to mutations in the PDE6C gene","volume":"106","author":"Chang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1086\/302423","article-title":"Homozygosity mapping of the Achromatopsia locus in the Pingelapese","volume":"64","author":"Winick","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.survophthal.2006.02.007","article-title":"Progressive Cone and Cone-Rod Dystrophies: Phenotypes and Underlying Molecular Genetic Basis","volume":"51","author":"Michaelides","year":"2006","journal-title":"Surv. Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1016\/j.addr.2005.09.003","article-title":"Wet age-related macular degeneration","volume":"57","author":"Kulkarni","year":"2005","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3897","DOI":"10.1167\/iovs.08-3153","article-title":"Photoreceptor protection by adeno-associated virus-mediated LEDGF expression in the RCS rat model of retinal degeneration: Probing the mechanism","volume":"50","author":"Zeng","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/mt.2008.301","article-title":"Improved Retinal Function in a Mouse Model of Dominant Retinitis Pigmentosa Following AAV-delivered Gene Therapy","volume":"17","author":"Chadderton","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1089\/hum.2009.119","article-title":"Adeno-Associated Virus-Mediated Rhodopsin Replacement Provides Therapeutic Benefit in Mice with a Targeted Disruption of the Rhodopsin Gene","volume":"21","author":"Palfi","year":"2010","journal-title":"Hum. Gene Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/jcp.22814","article-title":"Pluripotent human stem cells for the treatment of retinal disease","volume":"227","author":"Rowland","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.neuron.2011.07.015","article-title":"Regulated reprogramming in the regeneration of sensory receptor cells","volume":"71","author":"Reh","year":"2011","journal-title":"Neuron"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1097\/WCO.0b013e3283352f96","article-title":"Induced pluripotent stem cell therapies for retinal disease","volume":"23","author":"Comyn","year":"2010","journal-title":"Curr. Opin. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S0161-6420(02)01738-4","article-title":"Photoreceptor transplantation in retinitis pigmentosa: Short-term follow-up","volume":"110","author":"Berger","year":"2003","journal-title":"Ophthalmology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1002\/dneu.20914","article-title":"Optogenetics: A new enlightenment age for zebrafish neurobiology","volume":"72","author":"Wyart","year":"2012","journal-title":"Dev. Neurobiol."},{"key":"ref_23","first-page":"374","article-title":"Optogenetics for retinal disorders","volume":"9","author":"Henriksen","year":"2014","journal-title":"J. Ophthalmic Vis. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/cxo.12444","article-title":"Improvements in vision-related quality of life in blind patients implanted with the Argus II Epiretinal Prosthesis","volume":"100","author":"Duncan","year":"2017","journal-title":"Clin. Exp. Optom."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/j.ophtha.2015.04.032","article-title":"Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind","volume":"122","author":"Ho","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1089\/ars.2008.2171","article-title":"Increased expression of glutathione peroxidase 4 strongly protects retina from oxidative damage","volume":"11","author":"Lu","year":"2009","journal-title":"Antioxid. Redox Signal."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/mt.2009.47","article-title":"Increased expression of catalase and superoxide dismutase 2 reduces cone cell death in retinitis pigmentosa","volume":"17","author":"Usui","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nature05161","article-title":"Retinal repair by transplantation of photoreceptor precursors","volume":"444","author":"MacLaren","year":"2006","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.semcdb.2007.09.011","article-title":"Towards therapeutic application of ocular stem cells","volume":"18","author":"Pellegrini","year":"2007","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1007\/s12015-010-9192-8","article-title":"Stem Cell-Based Therapeutic Applications in Retinal Degenerative Diseases","volume":"7","author":"Huang","year":"2011","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/513287a","article-title":"Japan stem-cell trial stirs envy","volume":"513","author":"Reardon","year":"2014","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0140-6736(14)61376-3","article-title":"Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt\u2019s macular dystrophy: Follow-up of two open-label phase 1\/2 studies","volume":"385","author":"Schwartz","year":"2015","journal-title":"Lancet"},{"key":"ref_33","unstructured":"Takahashi, M., and Kurimoto, Y. (2017, February 15). Pilot Safety Study of iPSC-Based Intervention for Wet-Type AMD. Available online: http:\/\/www.riken-ibri.jp\/AMD\/english\/summary.html."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"16009","DOI":"10.1073\/pnas.0806114105","article-title":"Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin","volume":"105","author":"Lin","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/nn.2117","article-title":"Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration","volume":"11","author":"Lagali","year":"2008","journal-title":"Nat. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1038\/mt.2011.69","article-title":"Virally delivered channelrhodopsin-2 safely and effectively restores visual function in multiple mouse models of blindness","volume":"19","author":"Doroudchi","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Vaidya, A., Borgonovi, E., Taylor, R.S., Sahel, J.-A., Rizzo, S., Stanga, P.E., Kukreja, A., and Walter, P. (2014). The cost-effectiveness of the Argus II retinal prosthesis in retinitis pigmentosa patients. BMC Ophthalmol., 14.","DOI":"10.1186\/1471-2415-14-49"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1001\/archophthalmol.2011.2580","article-title":"\u03c9-3 Intake and visual acuity in patients with retinitis pigmentosa receiving vitamin A","volume":"130","author":"Berson","year":"2012","journal-title":"Arch. Ophthalmol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1001\/archopht.1993.01090060049022","article-title":"A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa","volume":"111","author":"Berson","year":"1993","journal-title":"Arch. Ophthalmol."},{"key":"ref_40","first-page":"704","article-title":"A randomized, placebo-controlled clinical trial of docosahexaenoic acid supplementation for X-linked retinitis pigmentosa","volume":"137","author":"Hoffman","year":"2004","journal-title":"Am. J. Ophthalmol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/S0022-2275(20)39729-7","article-title":"Red blood cell membrane phosphatidylethanolamine fatty acid content in various forms of retinitis pigmentosa","volume":"36","author":"Schaefer","year":"1995","journal-title":"J. Lipid Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11300","DOI":"10.1073\/pnas.0604056103","article-title":"Antioxidants reduce cone cell death in a model of retinitis pigmentosa","volume":"103","author":"Komeima","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1002\/jcp.21152","article-title":"Antioxidants slow photoreceptor cell death in mouse models of retinitis pigmentosa","volume":"213","author":"Komeima","year":"2007","journal-title":"J. Cell. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.preteyeres.2015.04.004","article-title":"The pros and cons of vertebrate animal models for functional and therapeutic research on inherited retinal dystrophies","volume":"48","author":"Slijkerman","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1038\/35103567","article-title":"The art and design of genetic screens: Zebrafish","volume":"2","author":"Patton","year":"2001","journal-title":"Nat. Rev. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/dvdy.1188","article-title":"Rod contributions to the electroretinogram of the dark-adapted developing zebrafish","volume":"222","author":"Bilotta","year":"2001","journal-title":"Dev. Dyn."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6009","DOI":"10.1073\/pnas.90.13.6009","article-title":"Zebrafish ultraviolet visual pigment: Absorption spectrum, sequence, and localization","volume":"90","author":"Robinson","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0012-1606(03)00125-8","article-title":"Development of a rod photoreceptor mosaic revealed in transgenic zebrafish","volume":"258","author":"Fadool","year":"2003","journal-title":"Dev. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Salbreux, G., Barthel, L.K., Raymond, P.A., and Lubensky, D.K. (2012). Coupling Mechanical Deformations and Planar Cell Polarity to Create Regular Patterns in the Zebrafish Retina. PLoS Comput. Biol., 8.","DOI":"10.1371\/journal.pcbi.1002618"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1002\/(SICI)1096-9861(20000117)416:3<356::AID-CNE7>3.0.CO;2-M","article-title":"Cell mosaic patterns in the native and regenerated inner retina of zebrafish: Implications for retinal assembly","volume":"416","author":"Cameron","year":"2000","journal-title":"J. Comp. Neurol."},{"key":"ref_51","unstructured":"Purves, D., Augustine, G., and Fitzpatrick, D. (2017, February 17). Anatomical Distribution of Rods and Cones, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK10848\/."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/BF00181769","article-title":"Count and density of human retinal photoreceptors","volume":"230","author":"Jonas","year":"1992","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/B978-0-12-384878-9.00007-8","article-title":"Toward a better understanding of human eye disease insights from the zebrafish, Danio rerio","volume":"100","author":"Bibliowicz","year":"2011","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1146\/annurev-vision-082114-035717","article-title":"Zebrafish Models of Retinal Disease","volume":"1","author":"Link","year":"2015","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/bdrc.20211","article-title":"The genetics of ocular disorders: Insights from the zebrafish","volume":"93","author":"Morris","year":"2011","journal-title":"Birth Defect. Res. Part C Embryo Today Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1002\/mrd.20831","article-title":"Zebrafish mutants as models for congenital ocular disorders in humans","volume":"75","author":"Gross","year":"2008","journal-title":"Mol. Reprod. Dev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s00018-010-0563-8","article-title":"Genetics of photoreceptor degeneration and regeneration in zebrafish","volume":"68","author":"Brockerhoff","year":"2011","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1387\/ijdb.041890mt","article-title":"Genetics of photoreceptor development and function in zebrafish","volume":"48","author":"Tsujikawa","year":"2004","journal-title":"Int. J. Dev. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Nakao, T., Tsujikawa, M., Notomi, S., Ikeda, Y., and Nishida, K. (2012). The Role of Mislocalized Phototransduction in Photoreceptor Cell Death of Retinitis Pigmentosa. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032472"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"13866","DOI":"10.1523\/JNEUROSCI.3136-07.2007","article-title":"A Mutation in the Cone-Specific pde6 Gene Causes Rapid Cone Photoreceptor Degeneration in Zebrafish","volume":"27","author":"Stearns","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1523\/JNEUROSCI.5019-09.2010","article-title":"Wild-Type Cone Photoreceptors Persist Despite Neighboring Mutant Cone Degeneration","volume":"30","author":"Lewis","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0042-6989(01)00146-8","article-title":"Retinal degeneration mutants in the mouse","volume":"42","author":"Chang","year":"2002","journal-title":"Vis. Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Owens, K.N., Santos, F., Roberts, B., Linbo, T., Coffin, A.B., Knisely, A.J., Simon, J.A., Rubel, E.W., and Raible, D.W. (2008). Identification of genetic and chemical modulators of zebrafish mechanosensory hair cell death. PLoS Genet., 4.","DOI":"10.1371\/journal.pgen.1000020"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"12965","DOI":"10.1073\/pnas.97.24.12965","article-title":"Small molecule developmental screens reveal the logic and timing of vertebrate development","volume":"97","author":"Peterson","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/nbt963","article-title":"Chemical suppression of a genetic mutation in a zebrafish model of aortic coarctation","volume":"22","author":"Peterson","year":"2004","journal-title":"Nat. Biotechnol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e109","DOI":"10.1016\/j.ddtec.2012.01.005","article-title":"Zebrafish-based small molecule screens for novel cardiovascular drugs","volume":"10","author":"Novodvorsky","year":"2013","journal-title":"Drug Discov. Today Technol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1126\/science.1183090","article-title":"Zebrafish behavioral profiling links drugs to biological targets and rest\/wake regulation","volume":"327","author":"Rihel","year":"2010","journal-title":"Science"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nchembio.307","article-title":"Rapid behavior-based identification of neuroactive small molecules in the zebrafish","volume":"6","author":"Kokel","year":"2010","journal-title":"Nat. Chem. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nchembio.2097","article-title":"Zebrafish behavioral profiling identifies multitarget antipsychotic-like compounds","volume":"12","author":"Bruni","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Dinday, M.T., and Baraban, S.C. (2015). Large-Scale Phenotype-Based Antiepileptic Drug Screening in a Zebrafish Model of Dravet Syndrome. eNeuro, 2.","DOI":"10.1523\/ENEURO.0068-15.2015"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1242\/dmm.018689","article-title":"Phenotype-driven chemical screening in zebrafish for compounds that inhibit collective cell migration identifies multiple pathways potentially involved in metastatic invasion","volume":"8","author":"Gallardo","year":"2015","journal-title":"Dis. Model. Mech."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1172\/JCI83831","article-title":"Progesterone receptor membrane component-1 regulates hepcidin biosynthesis","volume":"126","author":"Li","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.celrep.2015.01.010","article-title":"PTPMT1 inhibition lowers glucose through succinate dehydrogenase phosphorylation","volume":"10","author":"Nath","year":"2016","journal-title":"Cell Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"266ra170","DOI":"10.1126\/scitranslmed.3010189","article-title":"Visnagin protects against doxorubicin-induced cardiomyopathy through modulation of mitochondrial malate dehydrogenase","volume":"6","author":"Liu","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1177\/1087057112458153","article-title":"An in vivo zebrafish screen identifies organophosphate antidotes with diverse mechanisms of action","volume":"18","author":"Jin","year":"2013","journal-title":"J. Biomol. Screen."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/nchembio.1183","article-title":"Photochemical activation of TRPA1 channels in neurons and animals","volume":"9","author":"Kokel","year":"2013","journal-title":"Nat. Chem. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1096\/fj.12-225037","article-title":"Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure","volume":"27","author":"Nath","year":"2013","journal-title":"FASEB J."},{"key":"ref_78","first-page":"773","article-title":"Identification of compounds with anti-convulsant properties in a zebrafish model of epileptic seizures","volume":"5","author":"Baxendale","year":"2012","journal-title":"Dis. Model. Mech."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"19126","DOI":"10.1073\/pnas.0709337104","article-title":"OFF ganglion cells cannot drive the optokinetic reflex in zebrafish","volume":"104","author":"Emran","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Emran, F., Rihel, J., and Dowling, J.E. (2008). A behavioral assay to measure responsiveness of zebrafish to changes in light intensities. J. Vis. Exp., e923.","DOI":"10.3791\/923-v"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"8603","DOI":"10.1523\/JNEUROSCI.19-19-08603.1999","article-title":"Genetic disorders of vision revealed by a behavioral screen of 400 essential loci in zebrafish","volume":"19","author":"Neuhauss","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Muto, A., Orger, M.B., Wehman, A.M., Smear, M.C., Kay, J.N., Page-McCaw, P.S., Gahtan, E., Xiao, T., Nevin, L.M., and Gosse, N.J. (2005). Forward genetic analysis of visual behavior in zebrafish. PLoS Genet., 1.","DOI":"10.1371\/journal.pgen.0010066"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0166-4328(00)00264-3","article-title":"Effects of abnormal lighting on the development of zebrafish visual behavior","volume":"116","author":"Bilotta","year":"2000","journal-title":"Behav. Brain Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"10545","DOI":"10.1073\/pnas.92.23.10545","article-title":"A behavioral screen for isolating zebrafish mutants with visual system defects","volume":"92","author":"Brockerhoff","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/eye.2014.19","article-title":"Zebrafish\u2014on the move towards ophthalmological research","volume":"28","author":"Chhetri","year":"2014","journal-title":"Eye"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/dneu.20910","article-title":"Behavioral screening for neuroactive drugs in zebrafish","volume":"72","author":"Rihel","year":"2012","journal-title":"Dev. Neurobiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.conb.2009.10.007","article-title":"The neural basis of visual behaviors in the larval zebrafish","volume":"19","author":"Portugues","year":"2009","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0091-679X(04)77003-X","article-title":"Behavioral screening assays in zebrafish","volume":"77","author":"Orger","year":"2004","journal-title":"Methods Cell Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2448","DOI":"10.1038\/nprot.2006.255","article-title":"Measuring the optokinetic response of zebrafish larvae","volume":"1","author":"Brockerhoff","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4236","DOI":"10.1523\/JNEUROSCI.17-11-04236.1997","article-title":"A new form of inherited red-blindness identified in zebrafish","volume":"17","author":"Brockerhoff","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/(SICI)1098-2302(199712)31:4<267::AID-DEV4>3.0.CO;2-P","article-title":"The Development of Eye Movements in the Zebrafish (Danio rerio)","volume":"31","author":"Easter","year":"1997","journal-title":"Dev. Psychobiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1038\/80649","article-title":"Perception of Fourier and non-Fourier motion by larval zebrafish","volume":"3","author":"Baier","year":"2000","journal-title":"Nat. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1534\/genetics.104.039727","article-title":"Identification of zebrafish insertional mutants with defects in visual system development and function","volume":"170","author":"Gross","year":"2005","journal-title":"Genetics"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4584","DOI":"10.1073\/pnas.0307074101","article-title":"A zebrafish model for pyruvate dehydrogenase deficiency: Rescue of neurological dysfunction and embryonic lethality using a ketogenic diet","volume":"101","author":"Taylor","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ajhg.2014.06.012","article-title":"Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy","volume":"95","author":"Roosing","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.neuropharm.2015.03.022","article-title":"Effects of lorazepam and WAY-200070 in larval zebrafish light\/dark choice test","volume":"95","author":"Chen","year":"2015","journal-title":"Neuropharmacology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vascn.2013.09.002","article-title":"Early safety assessment of human oculotoxic drugs using the zebrafish visualmotor response","volume":"69","author":"Deeti","year":"2014","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.vascn.2008.04.002","article-title":"Validation of the use of zebrafish larvae in visual safety assessment","volume":"58","author":"Richards","year":"2008","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.2741\/2810","article-title":"The optokinetic response in zebrafish and its applications","volume":"13","author":"Huang","year":"2008","journal-title":"Front. Biosci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.compbiomed.2015.11.012","article-title":"Computational classification of different wild-type zebrafish strains based on their variation in light-induced locomotor response","volume":"69","author":"Gao","year":"2016","journal-title":"Comput. Biol. Med."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Liu, Y., Carmer, R., Zhang, G., Venkatraman, P., Brown, S.A., Pang, C.-P., Zhang, M., Ma, P., and Leung, Y.F. (2015). Statistical analysis of zebrafish locomotor response. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0139521"},{"key":"ref_102","unstructured":"(2017, May 23). Viewpoint LifeSciences. Available online: http:\/\/csl.mendeley.com\/styles\/485647231\/MDPI-LOGAN-FINAL."},{"key":"ref_103","unstructured":"(2017, May 23). Noldus. Available online: http:\/\/www.noldus.com."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1038\/nprot.2014.094","article-title":"Quantification of larval zebrafish motor function in multiwell plates using open-source MATLAB applications","volume":"9","author":"Zhou","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"11962","DOI":"10.1523\/JNEUROSCI.2848-10.2010","article-title":"Distinct Retinal Deficits in a Zebrafish Pyruvate Dehydrogenase-Deficient Mutant","volume":"30","author":"Maurer","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Zhang, L., Xiang, L., Liu, Y., Venkatraman, P., Chong, L., Cho, J., Bonilla, S., Jin, Z.-B., Pang, C.P., and Ko, K.M. (2016). A naturally-derived compound schisandrin B enhanced light sensation in the pde6c zebrafish model of retinal degeneration. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0154552"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3389\/fncir.2013.00109","article-title":"Quantification of locomotor activity in larval zebrafish: Considerations for the design of high-throughput behavioral studies","volume":"7","author":"Ingebretson","year":"2013","journal-title":"Front. Neural Circuits"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.beproc.2010.12.003","article-title":"Locomotor behaviors in zebrafish (Danio rerio) larvae","volume":"86","author":"Colwill","year":"2011","journal-title":"Behav. Processes"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1109\/TCBB.2014.2306829","article-title":"A high-throughput zebrafish screening method for visual mutants by light-induced locomotor response","volume":"11","author":"Gao","year":"2014","journal-title":"IEEE\/ACM Trans. Comput. Biol. Bioinforma."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.bbr.2011.11.020","article-title":"Behavioral profiling of zebrafish embryos exposed to a panel of 60 water-soluble compounds","volume":"228","author":"Ali","year":"2012","journal-title":"Behav. Brain Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.ntt.2012.03.002","article-title":"Locomotor activity assay in zebrafish larvae: Influence of age, strain and ethanol","volume":"34","author":"Slieker","year":"2012","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Ali, S., Mil, H.G.J.v., and Richardson, M.K. (2011). Large-Scale Assessment of the Zebrafish Embryo as a Possible Predictive Model in Toxicity Testing. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021076"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Lange, M., Neuzeret, F., Fabreges, B., Froc, C., Bedu, S., Bally-Cuif, L., and Norton, W.H.J. (2013). Inter-individual and inter-strain variations in zebrafish locomotor ontogeny. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070172"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1089\/zeb.2013.0871","article-title":"Systematic Screening of Behavioral Responses in Two Zebrafish Strains","volume":"10","author":"Vignet","year":"2013","journal-title":"Zebrafish"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.ntt.2011.08.005","article-title":"Assessing locomotor activity in larval zebrafish: Influence of extrinsic and intrinsic variables","volume":"33","author":"Padilla","year":"2011","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1016\/j.cub.2012.08.016","article-title":"Deep Brain Photoreceptors Control Light-Seeking Behavior in Zebrafish Larvae","volume":"22","author":"Fernandes","year":"2012","journal-title":"Curr. Biol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.reprotox.2013.06.067","article-title":"A category approach to predicting the developmental (neuro) toxicity of organotin compounds: The value of the zebrafish (Danio rerio) embryotoxicity test (ZET)","volume":"41","author":"Wolterbeek","year":"2013","journal-title":"Reprod. Toxicol."},{"key":"ref_118","first-page":"A120","article-title":"VideoHacking: Automated Tracking and Quantification of Locomotor Behavior with Open Source Software and Off-the-Shelf Video Equipment","volume":"13","author":"Conklin","year":"2015","journal-title":"J. Undergrad. Neurosci. Educ."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.pbb.2013.03.013","article-title":"iPhone\u00ae applications as versatile video tracking tools to analyze behavior in zebrafish (Danio rerio)","volume":"106","author":"Pittman","year":"2013","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1142\/S0219635212500057","article-title":"Automated visual choice discrimination learning in zebrafish (Danio rerio)","volume":"11","author":"Mueller","year":"2012","journal-title":"J. Integr. Neurosci."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Mueller, K.P., and Neuhauss, S.C.F. (2014). Sunscreen for Fish: Co-Option of UV Light Protection for Camouflage. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087372"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"4984","DOI":"10.1523\/JNEUROSCI.0615-07.2007","article-title":"Sensorimotor Gating in Larval Zebrafish","volume":"27","author":"Burgess","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_123","unstructured":"R Core Team (2017, May 15). R: A Language and Environment for Statistical Computing. Available online: http:\/\/www.r-project.org."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/cne.902510202","article-title":"Segmental homologies among reticulospinal neurons in the hindbrain of the zebrafish larva","volume":"251","author":"Metcalfe","year":"1986","journal-title":"J. Comp. Neurol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.1242\/jeb.003939","article-title":"Modulation of locomotor activity in larval zebrafish during light adaptation","volume":"210","author":"Burgess","year":"2007","journal-title":"J. Exp. Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1242\/jeb.66.1.65","article-title":"The Mauthner-initiated startle response in teleost fish","volume":"66","author":"Eaton","year":"1977","journal-title":"J. Exp. Biol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0896-6273(00)80783-7","article-title":"Laser ablations reveal functional relationships of segmental hindbrain neurons in zebrafish","volume":"23","author":"Liu","year":"1999","journal-title":"Neuron"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1242\/dev.128.11.2131","article-title":"The zebrafish space cadet gene controls axonal pathfinding of neurons that modulate fast turning movements","volume":"128","author":"Lorent","year":"2001","journal-title":"Development"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1017\/S0952523813000187","article-title":"The effects of nicotine on cone and rod b-wave responses in larval zebrafish","volume":"30","author":"Moyano","year":"2013","journal-title":"Vis. Neurosci."},{"key":"ref_130","first-page":"998","article-title":"Understanding the contribution of photoreceptors to the Visual Motor Response","volume":"56","author":"Venkatraman","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.neulet.2017.03.002","article-title":"Spectral properties of the zebrafish visual motor response","volume":"646","author":"Burton","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"4808","DOI":"10.1021\/acs.est.6b00223","article-title":"Parental Whole Life Cycle Exposure to Dietary Methylmercury in Zebrafish (Danio rerio) Affects the Behavior of Offspring","volume":"50","author":"Klingler","year":"2016","journal-title":"Environ. Sci. Technol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1097\/APO.0b013e31827a9969","article-title":"Drug Screening to Treat Early-Onset Eye Diseases","volume":"1","author":"Zhang","year":"2012","journal-title":"Asia Pac. J. Ophthalmol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/nmeth.2994","article-title":"idTracker: Tracking individuals in a group by automatic identification of unmarked animals","volume":"11","author":"Hinz","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Liu, Y., Ma, P., Cassidy, P., Carmer, R., Zhang, G., Venkatraman, P., Brown, S.A., Pang, C.-P., Zhong, W., and Zhang, M. (2017). Statistical analysis of zebrafish locomotor behaviour by logistic generalized linear mixed models. Sci. Rep., in press.","DOI":"10.1038\/s41598-017-02822-w"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/B978-0-12-384892-5.00011-6","article-title":"Monitoring Sleep and Arousal in Zebrafish","volume":"100","author":"Rihel","year":"2010","journal-title":"Methods Cell Biol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1002\/dvdy.24398","article-title":"Automated, high-throughput, in vivo analysis of visual function using the zebrafish","volume":"245","author":"Scott","year":"2016","journal-title":"Dev. Dyn."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1111\/j.1476-5381.2010.01127.x","article-title":"Principles of early drug discovery","volume":"162","author":"Hughes","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s00216-010-3933-z","article-title":"Cell-based assays: Fuelling drug discovery","volume":"398","author":"Michelini","year":"2010","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s12033-010-9251-z","article-title":"Cell-Based Assays for High-Throughput Screening","volume":"45","author":"An","year":"2010","journal-title":"Mol. Biotechnol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1177\/108705710100600202","article-title":"Cell-Based Versus Isolated Target Screening: How Lucky Do You Feel?","volume":"6","author":"Moore","year":"2001","journal-title":"J. Biomol. Screen"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"427","DOI":"10.3390\/ijms13010427","article-title":"Adaptation of High-Throughput Screening in Drug Discovery\u2014Toxicological Screening Tests","volume":"13","author":"Markowicz","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1158\/1535-7163.1365.3.11","article-title":"Discovery and mechanism of action of a novel series of apoptosis inducers with potential vascular targeting activity","volume":"3","author":"Kasibhatla","year":"2004","journal-title":"Mol. Cancer Ther."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1177\/1087057104265386","article-title":"Comparison of the Usefulness of the MTT, ATP, and Calcein Assays to Predict the Potency of Cytotoxic Agents in Various Human Cancer Cell Lines","volume":"9","author":"Mueller","year":"2004","journal-title":"J. Biomol. Screen"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1126\/science.287.5460.1960","article-title":"Drug discovery: A historical perspective","volume":"287","author":"Drews","year":"2000","journal-title":"Science"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S1359-6446(04)03316-1","article-title":"Target-based drug discovery: Is something wrong?","volume":"10","author":"Samsdodd","year":"2005","journal-title":"Drug Discov. Today"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/nrd2410","article-title":"Target deconvolution strategies in drug discovery","volume":"6","author":"Terstappen","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/clpt.2012.236","article-title":"Phenotypic vs. Target-Based Drug Discovery for First-in-Class Medicines","volume":"93","author":"Swinney","year":"2013","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nrd3480","article-title":"How were new medicines discovered?","volume":"10","author":"Swinney","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0014-2999(92)90855-X","article-title":"UCB L059, a novel anti-convulsant drug: Pharmacological profile in animals","volume":"222","author":"Gower","year":"1992","journal-title":"Eur. J. Pharmacol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"6034","DOI":"10.1073\/pnas.0914718107","article-title":"Zebrafish larvae lose vision at night","volume":"107","author":"Emran","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1073\/pnas.1112163109","article-title":"Extensive genetic diversity and substructuring among zebrafish strains revealed through copy number variant analysis","volume":"109","author":"Brown","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1007\/s10646-008-0267-0","article-title":"Genetic variation in strains of zebrafish (Danio rerio) and the implications for ecotoxicology studies","volume":"18","author":"Coe","year":"2009","journal-title":"Ecotoxicology"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1161\/01.ATV.0000068685.72914.7E","article-title":"Rapid Analysis of Angiogenesis Drugs in a Live Fluorescent Zebrafish Assay","volume":"23","author":"Cross","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"13991","DOI":"10.1038\/srep13991","article-title":"Multiplexed 3D FRET imaging in deep tissue of live embryos","volume":"5","author":"Zhao","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1002\/jbio.201500258","article-title":"Visualising apoptosis in live zebrafish using fluorescence lifetime imaging with optical projection tomography to map FRET biosensor activity in space and time","volume":"9","author":"Andrews","year":"2016","journal-title":"J. Biophotonics"},{"key":"ref_157","unstructured":"(2017, May 23). Pentair Aquatic Eco-Systems. Available online: http:\/\/pentairaes.com."},{"key":"ref_158","unstructured":"(2017, May 23). Techniplast. Available online: www.tecniplast.it."},{"key":"ref_159","unstructured":"(2017, May 23). Aquaneering Incorporated. Available online: http:\/\/www.aquaneering.com."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Adatto, I., Lawrence, C., Thompson, M., and Zon, L.I. (2011). A new system for the rapid collection of large numbers of developmentally staged zebrafish embryos. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021715"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1038\/nmeth.1481","article-title":"High-throughput in vivo vertebrate screening","volume":"7","author":"Chang","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1039\/C6LC00044D","article-title":"Fish-on-a-chip: Microfluidics for zebrafish research","volume":"16","author":"Yang","year":"2016","journal-title":"Lab Chip"},{"key":"ref_163","unstructured":"(2017, May 23). CSEM. Available online: http:\/\/www.csem.ch."},{"key":"ref_164","unstructured":"(2017, May 23). Union Biometrica. Available online: http:\/\/www.unionbio.com."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/6\/1185\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:37:49Z","timestamp":1760207869000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/6\/1185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,2]]},"references-count":164,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2017,6]]}},"alternative-id":["ijms18061185"],"URL":"https:\/\/doi.org\/10.3390\/ijms18061185","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,2]]}}}