{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:57:58Z","timestamp":1791928678187,"version":"4.3.4"},"reference-count":112,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"7","license":[{"start":{"date-parts":[[2018,6,11]],"date-time":"2018-06-11T00:00:00Z","timestamp":1528675200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2018,6,11]]},"DOI":"10.1167\/iovs.18-23829","type":"journal-article","created":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T19:20:04Z","timestamp":1532114404000},"page":"2999","source":"Crossref","is-referenced-by-count":17,"title":["D-\n                    <i>cis<\/i>\n                    -Diltiazem Can Produce Oxidative Stress in Healthy Depolarized Rods In Vivo"],"prefix":"10.1167","volume":"59","author":[{"given":"Bruce A.","family":"Berkowitz","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States"},{"name":"Department of Ophthalmology, Wayne State University School of Medicine, Detroit, Michigan, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Podolsky","sequence":"additional","affiliation":[{"name":"Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Farrell","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hojun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Trepanier","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali M.","family":"Berri","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Dernay","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Graffice","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatema","family":"Shafie-Khorassani","sequence":"additional","affiliation":[{"name":"Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy S.","family":"Kern","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"i1552-5783-59-7-2999-b01","doi-asserted-by":"crossref","unstructured":"Baumann L, Gerstner A, Zong X, Biel M, Wahl-Schott C. Functional characterization of the L-type Ca2+ channel Cav1.4a1 from mouse retina. Invest Ophthalmol Vis Sci. 2004; 45: 708\u2013713.","DOI":"10.1167\/iovs.03-0937"},{"key":"i1552-5783-59-7-2999-b02","doi-asserted-by":"crossref","unstructured":"Tarabova B, Lacinova L, Engel J. Effects of phenylalkylamines and benzothiazepines on Cav1.3-mediated Ca2+ currents in neonatal mouse inner hair cells. Eur J Pharmocol. 2007; 573: 39\u201348.","DOI":"10.1016\/j.ejphar.2007.06.050"},{"key":"i1552-5783-59-7-2999-b03","doi-asserted-by":"crossref","unstructured":"Berkowitz BA, Grady EM, Roberts R. Confirming a prediction of the calcium hypothesis of photoreceptor aging in mice. Neurobiol Aging. 2014; 35: 1883\u20131891.","DOI":"10.1016\/j.neurobiolaging.2014.02.020"},{"key":"i1552-5783-59-7-2999-b04","doi-asserted-by":"crossref","unstructured":"Bissig D, Goebel D, Berkowitz BA. Diminished vision in healthy aging is associated with increased retinal L-type voltage gated calcium channel ion influx. PLoS One. 2013; 8: e56340.","DOI":"10.1371\/journal.pone.0056340"},{"key":"i1552-5783-59-7-2999-b05","doi-asserted-by":"crossref","unstructured":"Glossmann H, Linn T, Rombusch M, Ferry DR. Temperature-dependent regulation of d-cis-[3H]diltiazem binding to Ca2+ channels by 1,4-dihydropyridine channel agonists and antagonists. FEBS Lett. 1983; 160: 226\u2013232.","DOI":"10.1016\/0014-5793(83)80972-7"},{"key":"i1552-5783-59-7-2999-b06","doi-asserted-by":"crossref","unstructured":"Shi L, Chang JY-A, Yu F, Ko ML, Ko GY-P. The contribution of L-type Cav1.3 channels to retinal light responses. Front Mol Neurosci. 2017; 10: 394.","DOI":"10.3389\/fnmol.2017.00394"},{"key":"i1552-5783-59-7-2999-b07","doi-asserted-by":"crossref","unstructured":"Frasson M, Sahel JA, Fabre M, Simonutti M, Dreyfus H, Picaud S. Retinitis pigmentosa: rod photoreceptor rescue by a calcium-channel blocker in the rd mouse. Nat Med. 1999; 5: 1183\u20131187.","DOI":"10.1038\/13508"},{"key":"i1552-5783-59-7-2999-b08","doi-asserted-by":"crossref","unstructured":"Sanges D, Comitato A, Tammaro R, Marigo V. Apoptosis in retinal degeneration involves cross-talk between apoptosis-inducing factor (AIF) and caspase-12 and is blocked by calpain inhibitors. Proc Natl Acad Sci U S A. 2006; 103: 17366\u201317371.","DOI":"10.1073\/pnas.0606276103"},{"key":"i1552-5783-59-7-2999-b09","doi-asserted-by":"crossref","unstructured":"Read DS, McCall MA, Gregg RG. Absence of voltage-dependent calcium channels delays photoreceptor degeneration in rd mice. Exp Eye Res. 2002; 75: 415\u2013420.","DOI":"10.1006\/exer.2002.2034"},{"key":"i1552-5783-59-7-2999-b10","doi-asserted-by":"crossref","unstructured":"Cia D, Bordais A, Varela C, et al. Voltage-gated channels and calcium homeostasis in mammalian rod photoreceptors. J Neurophysiol. 2005; 93: 1468\u20131475.","DOI":"10.1152\/jn.00874.2004"},{"key":"i1552-5783-59-7-2999-b11","doi-asserted-by":"crossref","unstructured":"Vallazza-Deschamps G, Cia D, Gong J, et al. Excessive activation of cyclic nucleotide-gated channels contributes to neuronal degeneration of photoreceptors. Eur J Neurosci. 2005; 22: 1013\u20131022.","DOI":"10.1111\/j.1460-9568.2005.04306.x"},{"key":"i1552-5783-59-7-2999-b12","doi-asserted-by":"crossref","unstructured":"Fox DA, Poblenz AT, He L. Calcium overload triggers rod photoreceptor apoptotic cell death in chemical-induced and inherited retinal degenerations. Ann N Y Acad Sci. 1999; 893: 282\u2013285.","DOI":"10.1111\/j.1749-6632.1999.tb07837.x"},{"key":"i1552-5783-59-7-2999-b13","doi-asserted-by":"crossref","unstructured":"Nakazawa M. Effects of calcium ion, calpains, and calcium channel blockers on retinitis pigmentosa. J Ophthalmol. 2011; 2011: 292040.","DOI":"10.1155\/2011\/292040"},{"key":"i1552-5783-59-7-2999-b14","doi-asserted-by":"crossref","unstructured":"Sch\u00f6n C, Paquet-Durand F, Michalakis S. Ca(v)1.4 L-type calcium channels contribute to calpain activation in degenerating photoreceptors of rd1 Mice. PLoS One. 2016; 11: e0156974.","DOI":"10.1371\/journal.pone.0156974"},{"key":"i1552-5783-59-7-2999-b15","doi-asserted-by":"crossref","unstructured":"Pasantes-Morales H, Quiroz H, Quesada O. Treatment with taurine, diltiazem, and vitamin E retards the progressive visual field reduction in retinitis pigmentosa: a 3-year follow-up study. Metab Brain Dis. 2002; 17: 183\u2013197.","DOI":"10.1023\/A:1019926122125"},{"key":"i1552-5783-59-7-2999-b16","unstructured":"Pawlyk BS, Li T, Scimeca MS, Sandberg MA, Berson EL. Absence of photoreceptor rescue with d-cis-diltiazem in the rd mouse. Invest Ophthalmol Vis Sci. 2002; 43: 1912\u20131915."},{"key":"i1552-5783-59-7-2999-b17","unstructured":"Bush RA, Kononen L, Machida S, Sieving PA. The effect of calcium channel blocker diltiazem on photoreceptor degeneration in the rhodopsin Pro23His rat. Invest Ophthalmol Vis Sci. 2000; 41: 2697\u20132701."},{"key":"i1552-5783-59-7-2999-b18","doi-asserted-by":"crossref","unstructured":"Ma EY, Lewis A, Barabas P, et al. Loss of Pde6 reduces cell body Ca(2+) transients within photoreceptors. Cell Death Dis. 2013; 4: e797.","DOI":"10.1038\/cddis.2013.332"},{"key":"i1552-5783-59-7-2999-b19","unstructured":"Pearce-Kelling SE, Aleman TS, Nickle A, et al. Calcium channel blocker D-cis-diltiazem does not slow retinal degeneration in the PDE6B mutant rcd1 canine model of retinitis pigmentosa. Mol Vis. 2001; 7: 42\u201347."},{"key":"i1552-5783-59-7-2999-b20","unstructured":"Yamazaki H, Ohguro H, Maeda T, et al. Preservation of retinal morphology and functions in Royal College Surgeons rat by nilvadipine, a Ca2+ antagonist. Invest Ophthalmol Vis Sci. 2002; 43: 919\u2013926."},{"key":"i1552-5783-59-7-2999-b21","doi-asserted-by":"crossref","unstructured":"Takano Y, Ohguro H, Dezawa M, et al. Study of drug effects of calcium channel blockers on retinal degeneration of rd mouse. Biochem Biophys Res Commun. 2004; 313: 1015\u20131022.","DOI":"10.1016\/j.bbrc.2003.12.034"},{"key":"i1552-5783-59-7-2999-b22","doi-asserted-by":"crossref","unstructured":"Usui S, Oveson BC, Lee SY, et al. NADPH oxidase plays a central role in cone cell death in retinitis pigmentosa. J Neurochem. 2009; 110: 1028\u20131037.","DOI":"10.1111\/j.1471-4159.2009.06195.x"},{"key":"i1552-5783-59-7-2999-b23","doi-asserted-by":"crossref","unstructured":"Hart J, Wilkinson MF, Kelly MEM, Barnes S. Inhibitory action of diltiazem on voltage-gated calcium channels in cone photoreceptors. Exp Eye Res. 2003; 76: 597\u2013604.","DOI":"10.1016\/S0014-4835(03)00027-7"},{"key":"i1552-5783-59-7-2999-b24","doi-asserted-by":"crossref","unstructured":"Koch KW, Kaupp UB. Cyclic GMP directly regulates a cation conductance in membranes of bovine rods by a cooperative mechanism. J Biol Chem. 1985; 260: 6788\u20136800.","DOI":"10.1016\/S0021-9258(18)88849-4"},{"key":"i1552-5783-59-7-2999-b25","doi-asserted-by":"crossref","unstructured":"Berkowitz BA, Murphy GG, Craft CM, Surmeier DJ, Roberts R. Genetic dissection of horizontal cell inhibitory signaling in mice in complete darkness in vivo. Invest Ophthalmol Vis Sci. 2015; 56: 3132\u20133139.","DOI":"10.1167\/iovs.15-16581"},{"key":"i1552-5783-59-7-2999-b26","doi-asserted-by":"crossref","unstructured":"Berkowitz BA, Bissig D, Roberts R. MRI of rod cell compartment-specific function in disease and treatment in svivo. Prog Retin Eye Res. 2016; 51: 90\u2013106.","DOI":"10.1016\/j.preteyeres.2015.09.001"},{"key":"i1552-5783-59-7-2999-b27","doi-asserted-by":"crossref","unstructured":"Ramos de Carvalho JE, Verbraak FD, Aalders MC, van Noorden CJ, Schlingemann RO. Recent advances in ophthalmic molecular imaging. Surv Ophthalmol. 2014; 59: 393\u2013413.","DOI":"10.1016\/j.survophthal.2013.09.005"},{"key":"i1552-5783-59-7-2999-b28","doi-asserted-by":"crossref","unstructured":"Sinnegger-Brauns MJ, Huber IG, Koschak A, et al. Expression and 1,4-dihydropyridine-binding properties of brain l-type calcium channel isoforms. Mol Pharmacol. 2009; 75: 407\u2013414.","DOI":"10.1124\/mol.108.049981"},{"key":"i1552-5783-59-7-2999-b29","doi-asserted-by":"crossref","unstructured":"Sinnegger-Brauns MJ, Hetzenauer A, Huber IG, et al. Isoform-specific regulation of mood behavior and pancreatic beta cell and cardiovascular function by L-type Ca 2+ channels. J Clin Invest. 2004; 113: 1430\u20131439.","DOI":"10.1172\/JCI20208"},{"key":"i1552-5783-59-7-2999-b30","doi-asserted-by":"crossref","unstructured":"Kang K, Tarchick MJ, Yu X, Beight C, Bu P, Yu M. Carnosic acid slows photoreceptor degeneration in the Pde6b(rd10) mouse model of retinitis pigmentosa. Sci Rep. 2016; 6: 22632.","DOI":"10.1038\/srep22632"},{"key":"i1552-5783-59-7-2999-b31","doi-asserted-by":"crossref","unstructured":"Oveson BC, Iwase T, Hackett SF, et al. Constituents of bile, bilirubin and TUDCA, protect against oxidative stress-induced retinal degeneration. J Neurochem. 2011; 116: 144\u2013153.","DOI":"10.1111\/j.1471-4159.2010.07092.x"},{"key":"i1552-5783-59-7-2999-b32","doi-asserted-by":"crossref","unstructured":"Galbinur T, Obolensky A, Berenshtein E, et al. Effect of para-aminobenzoic acid on the course of retinal degeneration in the rd10 mouse. J Ocul Pharmacol Ther. 2009; 25: 475\u2013482.","DOI":"10.1089\/jop.2009.0020"},{"key":"i1552-5783-59-7-2999-b33","doi-asserted-by":"crossref","unstructured":"Shen J, Yang X, Dong A, et al. Oxidative damage is a potential cause of cone cell death in retinitis pigmentosa. J Cell Physiol. 2005; 203: 457\u2013464.","DOI":"10.1002\/jcp.20346"},{"key":"i1552-5783-59-7-2999-b34","doi-asserted-by":"crossref","unstructured":"Yu DY, Cringle S, Valter K, Walsh N, Lee D, Stone J. Photoreceptor death, trophic factor expression, retinal oxygen status, and photoreceptor function in the P23H rat. Invest Ophthalmol Vis Sci. 2004; 45: 2013\u20132019.","DOI":"10.1167\/iovs.03-0845"},{"key":"i1552-5783-59-7-2999-b35","unstructured":"Rajaraman G, Wang G, Smith HJ, Gong Y, Burczynski FJ. Effect of diltiazem isomers and thiamine on piglet liver microsomal peroxidation using dichlorofluorescein. J Pharm Pharm Sci. 2007; 10: 380\u2013387."},{"key":"i1552-5783-59-7-2999-b36","doi-asserted-by":"crossref","unstructured":"Castro J, Hughes R, Smith H, Barritt GJ. Diltiazem protects hepatocytes from damage induced by reactive oxygen species through actions on mitochondria. J Gastroenterol Hepatol Res. 2016: 5: 1977\u20131983.","DOI":"10.17554\/j.issn.2224-3992.2016.05.568"},{"key":"i1552-5783-59-7-2999-b37","doi-asserted-by":"crossref","unstructured":"Velena A, Zarkovic N, Gall Troselj K, et al. 1,4-dihydropyridine derivatives: dihydronicotinamide analogues\u2014model compounds targeting oxidative stress. Oxid Med Cell Longev. 2016; 2016: 1892412.","DOI":"10.1155\/2016\/1892412"},{"key":"i1552-5783-59-7-2999-b38","doi-asserted-by":"crossref","unstructured":"Morakinyo A, Iranloye B, Adegoke O. Calcium antagonists modulate oxidative stress and acrosomal reaction in rat spermatozoa. Arch Med Sci. 2011; 7: 613\u2013618.","DOI":"10.5114\/aoms.2011.24130"},{"key":"i1552-5783-59-7-2999-b39","unstructured":"Okwa IB, Akindele AJ, Agbaje EO, Oshinuga OT, Anunobi CC, Adeyemi OO. Effect of subclinical, clinical and supraclinical doses of calcium channel blockers on models of drug-induced hepatotoxicity in rats. EXCLI J. 2013; 12: 231\u2013250."},{"key":"i1552-5783-59-7-2999-b40","doi-asserted-by":"crossref","unstructured":"Farghali H, Kmonickova E, Lotkova H, Martinek J. Evaluation of calcium channel blockers as potential hepatoprotective agents in oxidative stress injury of perfused hepatocytes. Physiol Res. 2000; 49: 261\u2013268.","DOI":"10.33549\/physiolres.930000.49.261"},{"key":"i1552-5783-59-7-2999-b41","doi-asserted-by":"crossref","unstructured":"Berkowitz BA, Podolsky RH, Lenning J, et al. Sodium iodate produces a strain-dependent retinal oxidative stress response measured in vivo using QUEST MRI. Invest Ophthalmol Vis Sci. 2017; 58: 3286\u20133293.","DOI":"10.1167\/iovs.17-21850"},{"key":"i1552-5783-59-7-2999-b42","doi-asserted-by":"crossref","unstructured":"Berkowitz BA, Lewin AS, Biswal MR, Bredell BX, Davis C, Roberts R. MRI of retinal free radical production with laminar resolution in vivo. Invest Ophthalmol Vis Sci. 2016; 57: 577\u2013585.","DOI":"10.1167\/iovs.15-18972"},{"key":"i1552-5783-59-7-2999-b43","doi-asserted-by":"crossref","unstructured":"Berkowitz BA, Bredell BX, Davis C, Samardzija M, Grimm C, Roberts R. Measuring in vivo free radical production by the outer retina. Invest Ophthalmol Vis Sci. 2015; 56: 7931\u20137938.","DOI":"10.1167\/iovs.15-18420"},{"key":"i1552-5783-59-7-2999-b44","doi-asserted-by":"crossref","unstructured":"Berkowitz BA, Lenning J, Khetarpal N, et al. In vivo imaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome. FASEB J. 2017; 31: 4179\u20134186.","DOI":"10.1096\/fj.201700229R"},{"key":"i1552-5783-59-7-2999-b45","doi-asserted-by":"crossref","unstructured":"Striessnig J, Koschak A, Sinnegger-Brauns MJ, et al. Role of voltage-gated L-type Ca2+ channel isoforms for brain function. Biochem Soc Trans. 2006; 34: 903\u2013909.","DOI":"10.1042\/BST0340903"},{"key":"i1552-5783-59-7-2999-b46","doi-asserted-by":"crossref","unstructured":"Zhang J, Berra-Romani R, Sinnegger-Brauns MJ, Striessnig J, Blaustein MP, Matteson DR. Role of Cav1.2 L-type Ca2+ channels in vascular tone: effects of nifedipine and Mg2+. Am J Physiol Heart Circ Physiol. 2007; 292: H415\u2013H425.","DOI":"10.1152\/ajpheart.01214.2005"},{"key":"i1552-5783-59-7-2999-b47","doi-asserted-by":"crossref","unstructured":"Lipscombe D, Andrade A, Allen SE. Alternative splicing: functional diversity among voltage-gated calcium channels and behavioral consequences. Biochim Biophys Acta. 2013; 1828: 1522\u20131529.","DOI":"10.1016\/j.bbamem.2012.09.018"},{"key":"i1552-5783-59-7-2999-b48","unstructured":"Jurkovicova-Tarabova B, Griesemer D, Pirone A, Sinnegger-Brauns MJ, Striessnig J, Friauf E. Repertoire of high voltage-activated Ca2+ channels in the lateral superior olive: functional analysis in wild-type, Ca(v)1.3(-\/-), and Ca(v)1.2DHP(-\/-) mice. J Neurophysiol. 2012; 108: 365\u2013379."},{"key":"i1552-5783-59-7-2999-b49","doi-asserted-by":"crossref","unstructured":"Oz M, Lorke DE, Hasan M, Petroianu GA. Cellular and molecular actions of Methylene Blue in the nervous system. Med Res Rev. 2011; 31: 93\u2013117.","DOI":"10.1002\/med.20177"},{"key":"i1552-5783-59-7-2999-b50","doi-asserted-by":"crossref","unstructured":"Packer L. Antioxidant properties of lipoic acid and its therapeutic effects in prevention of diabetes complications and cataracts. Ann N Y Acad Sci. 1994; 738: 257\u2013264.","DOI":"10.1111\/j.1749-6632.1994.tb21811.x"},{"key":"i1552-5783-59-7-2999-b51","unstructured":"Haacke EM, Brown RW, Thompson MR, Venkatesan R. Magnetic Resonance Imaging: Physical Principles and Sequence Design. New York: Wiley; 1999."},{"key":"i1552-5783-59-7-2999-b52","doi-asserted-by":"crossref","unstructured":"Bissig D, Berkowitz BA. Same-session functional assessment of rat retina and brain with manganese-enhanced MRI. NeuroImage. 2011; 58: 749\u2013760.","DOI":"10.1016\/j.neuroimage.2011.06.062"},{"key":"i1552-5783-59-7-2999-b53","doi-asserted-by":"crossref","unstructured":"Cheng H, Nair G, Walker TA, et al. Structural and functional MRI reveals multiple retinal layers. Proc Natl Acad Sci U S A. 2006; 103: 17525\u201317530.","DOI":"10.1073\/pnas.0605790103"},{"key":"i1552-5783-59-7-2999-b54","doi-asserted-by":"crossref","unstructured":"Berkowitz BA, Grady EM, Khetarpal N, Patel A, Roberts R. Oxidative stress and light-evoked responses of the posterior segment in a mouse model of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2015; 56: 606\u2013615.","DOI":"10.1167\/iovs.14-15687"},{"key":"i1552-5783-59-7-2999-b55","unstructured":"Xiao H, Chen X, Steele EC Jr. Abundant L-type calcium channel Ca(v)1.3 (alpha1D) subunit mRNA is detected in rod photoreceptors of the mouse retina via in situ hybridization. Mol Vis. 2007; 13: 764\u2013771."},{"key":"i1552-5783-59-7-2999-b56","doi-asserted-by":"crossref","unstructured":"Fox DA, Poblenz AT, He L, Harris JB, Medrano CJ. Pharmacological strategies to block rod photoreceptor apoptosis caused by calcium overload: a mechanistic target-site approach to neuroprotection. Eur J Ophthalmol. 2003; 13 (Suppl 3): S44\u2013S56.","DOI":"10.1177\/112067210301303S08"},{"key":"i1552-5783-59-7-2999-b57","doi-asserted-by":"crossref","unstructured":"Barabas P, Cutler PC, Krizaj D. Do calcium channel blockers rescue dying photoreceptors in the Pde6b (rd1) mouse? Adv Exp Med Biol. 2010; 664: 491\u2013499.","DOI":"10.1007\/978-1-4419-1399-9_56"},{"key":"i1552-5783-59-7-2999-b58","doi-asserted-by":"crossref","unstructured":"Ko ML, Liu Y, Dryer SE, Ko GY-P. The expression of L-type voltage-gated calcium channels in retinal photoreceptors is under circadian control. J Neurochem. 2007; 103: 784\u2013792.","DOI":"10.1111\/j.1471-4159.2007.04816.x"},{"key":"i1552-5783-59-7-2999-b59","doi-asserted-by":"crossref","unstructured":"Firth SI, Morgan IG, Boelen MK, Morgans CW. Localization of voltage-sensitive L-type calcium channels in the chicken retina. Clin Exp Ophthalmol. 2001; 29: 183\u2013187.","DOI":"10.1046\/j.1442-9071.2001.00401.x"},{"key":"i1552-5783-59-7-2999-b60","doi-asserted-by":"crossref","unstructured":"Xu HP, Zhao JW, Yang XL. Expression of voltage-dependent calcium channel subunits in the rat retina. Neurosci Lett. 2002; 329: 297\u2013300.","DOI":"10.1016\/S0304-3940(02)00688-2"},{"key":"i1552-5783-59-7-2999-b61","doi-asserted-by":"crossref","unstructured":"Zou J, Lee A, Yang J. The expression of whirlin and Cav1.3a1 is mutually independent in photoreceptors. Vision Res. 2012; 75: 53\u201359.","DOI":"10.1016\/j.visres.2012.07.020"},{"key":"i1552-5783-59-7-2999-b62","doi-asserted-by":"crossref","unstructured":"Busquet P, Khoi Nguyen N, Schmid E, et al. CaV1.3 L-type Ca2+ channels modulate depression-like behaviour in mice independent of deaf phenotype. Int J Neuropsychopharmacol. 2010; 13: 499\u2013513.","DOI":"10.1017\/S1461145709990368"},{"key":"i1552-5783-59-7-2999-b63","unstructured":"Carter-Dawson LD, Lavail MM, Sidman RL. Differential effect of the rd mutation on rods and cones in the mouse retina. Invest Ophthalmol Vis Sci. 1978; 17: 489\u2013498."},{"key":"i1552-5783-59-7-2999-b64","doi-asserted-by":"crossref","unstructured":"Tain RW, Scotti AM, Li W, Zhou XJ, Cai K. Imaging short-lived reactive oxygen species (ROS) with endogenous contrast MRI. J Magn Reson Imaging. 2018; 47: 222\u2013229.","DOI":"10.1002\/jmri.25763"},{"key":"i1552-5783-59-7-2999-b65","unstructured":"Stinnett G, Moore K, Samuel E, et al. A novel assay for the in vivo detection of reactive oxygen species using MRI. ISMRM Meeting Abstracts. 2015; 1917."},{"key":"i1552-5783-59-7-2999-b66","doi-asserted-by":"crossref","unstructured":"Bakalova R, Georgieva E, Ivanova D, Zhelev Z, Aoki I, Saga T. Magnetic resonance imaging of mitochondrial dysfunction and metabolic activity, accompanied by overproduction of superoxide. ACS Chem Neurosci. 2015; 6: 1922\u20131929.","DOI":"10.1021\/acschemneuro.5b00220"},{"key":"i1552-5783-59-7-2999-b67","unstructured":"Johnson JE Jr, Perkins GA, Giddabasappa A, et al. Spatiotemporal regulation of ATP and Ca2+ dynamics in vertebrate rod and cone ribbon synapses. Mol Vis. 2007; 13: 887\u2013919."},{"key":"i1552-5783-59-7-2999-b68","doi-asserted-by":"crossref","unstructured":"Molden E, Johansen PW, Boe GH, et al. Pharmacokinetics of diltiazem and its metabolites in relation to CYP2D6 genotype. Clin Pharmacol Ther. 2002; 72: 333\u2013342.","DOI":"10.1067\/mcp.2002.127396"},{"key":"i1552-5783-59-7-2999-b69","doi-asserted-by":"crossref","unstructured":"Zangar RC, Davydov DR, Verma S. Mechanisms that regulate production of reactive oxygen species by cytochrome P450. Toxicol Appl Pharmacol. 2004; 199: 316\u2013331.","DOI":"10.1016\/j.taap.2004.01.018"},{"key":"i1552-5783-59-7-2999-b70","doi-asserted-by":"crossref","unstructured":"Lee Y-H, Lee M-H, Shim C-K. Pharmacokinetics of diltiazem and deacetyldiltiazem in rats. Int J Pharm. 1991; 76: 71\u201376.","DOI":"10.1016\/0378-5173(91)90345-O"},{"key":"i1552-5783-59-7-2999-b71","doi-asserted-by":"crossref","unstructured":"Nakano M, Lockhart CM, Kelly EJ, Rettie AE. Ocular cytochrome P450s and transporters: roles in disease and endobiotic and xenobiotic disposition. Drug Metab Rev. 2014; 46: 247\u2013260.","DOI":"10.3109\/03602532.2014.921190"},{"key":"i1552-5783-59-7-2999-b72","doi-asserted-by":"crossref","unstructured":"Toselli F, Dodd PR, Gillam EMJ. Emerging roles for brain drug-metabolizing cytochrome P450 enzymes in neuropsychiatric conditions and responses to drugs. Drug Metab Rev. 2016; 48: 379\u2013404.","DOI":"10.1080\/03602532.2016.1221960"},{"key":"i1552-5783-59-7-2999-b73","doi-asserted-by":"crossref","unstructured":"Wang K, Chen S, Xie W, Wan Y-JY. Retinoids induce cytochrome P450 3A4 through RXR\/VDR-mediated Pathway. Biochem Pharmacol. 2008; 75: 2204\u20132213.","DOI":"10.1016\/j.bcp.2008.02.030"},{"key":"i1552-5783-59-7-2999-b74","doi-asserted-by":"crossref","unstructured":"Hong S-P, Choi D-H, Choi J-S. Effects of resveratrol on the pharmacokinetics of diltiazem and its major metabolite, desacetyldiltiazem, in rats. Cardiovasc Therap. 2008; 26: 269\u2013275.","DOI":"10.1111\/j.1755-5922.2008.00060.x"},{"key":"i1552-5783-59-7-2999-b75","doi-asserted-by":"crossref","unstructured":"Szikra T, Barabas P, Bartoletti TM, et al. Calcium homeostasis and cone signaling are regulated by interactions between calcium stores and plasma membrane ion channels. PLoS One. 2009; 4: e6723.","DOI":"10.1371\/journal.pone.0006723"},{"key":"i1552-5783-59-7-2999-b76","doi-asserted-by":"crossref","unstructured":"Guerra L, Cerbai E, Gessi S, Borea PA, Mugelli A. The effect of oxygen free radicals on calcium current and dihydropyridine binding sites in guinea-pig ventricular myocytes. Br J Pharmacol. 1996; 118: 1278\u20131284.","DOI":"10.1111\/j.1476-5381.1996.tb15534.x"},{"key":"i1552-5783-59-7-2999-b77","doi-asserted-by":"crossref","unstructured":"Kooragayala K, Gotoh N, Cogliati T, et al. Quantification of oxygen consumption in retina ex vivo demonstrates limited reserve capacity of photoreceptor mitochondria. Invest Ophthalmol Vis Sci. 2015; 56: 8428\u20138436.","DOI":"10.1167\/iovs.15-17901"},{"key":"i1552-5783-59-7-2999-b78","doi-asserted-by":"crossref","unstructured":"Cingolani C, Rogers B, Lu L, Kachi S, Shen J, Campochiaro PA. Retinal degeneration from oxidative damage. Free Radic Biol Med. 2006; 40: 660\u2013669.","DOI":"10.1016\/j.freeradbiomed.2005.09.032"},{"key":"i1552-5783-59-7-2999-b79","doi-asserted-by":"crossref","unstructured":"Witola WH, Kim CY, Zhang X. Inherent oxidative stress in the Lewis Rat is associated with resistance to toxoplasmosis. Infect Immun. 2017; 85: e00289\u201317.","DOI":"10.1128\/IAI.00289-17"},{"key":"i1552-5783-59-7-2999-b80","doi-asserted-by":"crossref","unstructured":"Battelle BA, LaVail MM. Rhodopsin content and rod outer segment length in albino rat eyes: modification by dark adaptation. Exp Eye Res. 1978; 26: 487\u2013497.","DOI":"10.1016\/0014-4835(78)90134-3"},{"key":"i1552-5783-59-7-2999-b81","doi-asserted-by":"crossref","unstructured":"Sondereker KB, Onyak JR, Islam SW, Ross CL, Renna JM. Melanopsin ganglion cell outer retinal dendrites: morphologically distinct and asymmetrically distributed in the mouse retina. J Comp Neurol. 2017; 525: 3653\u20133665.","DOI":"10.1002\/cne.24293"},{"key":"i1552-5783-59-7-2999-b82","doi-asserted-by":"crossref","unstructured":"Ortin-Martinez A, Nadal-Nicolas FM, Jimenez-Lopez M, et al. Number and distribution of mouse retinal cone photoreceptors: differences between an albino (Swiss) and a pigmented (C57\/BL6) strain. PLoS One. 2014; 9: e102392.","DOI":"10.1371\/journal.pone.0102392"},{"key":"i1552-5783-59-7-2999-b83","unstructured":"Zhu Y, Natoli R, Valter K, Stone J. Differential gene expression in mouse retina related to regional differences in vulnerability to hyperoxia. Mol Vis. 2010; 16: 740\u2013755."},{"key":"i1552-5783-59-7-2999-b84","unstructured":"Howell WL, Rapp LM, Williams TP. Distribution of melanosomes across the retinal pigment epithelium of a hooded rat: implications for light damage. Invest Ophthalmol Vis Sci. 1982; 22: 139\u2013144."},{"key":"i1552-5783-59-7-2999-b85","unstructured":"Williams MA, Pinto LH, Gherson J. The retinal pigment epithelium of wild type (C57BL\/6J +\/+) and pearl mutant (C57BL\/6J pe\/pe) mice. Invest Ophthalmol Vis Sci. 1985; 26: 657\u2013669."},{"key":"i1552-5783-59-7-2999-b86","doi-asserted-by":"crossref","unstructured":"Polosa A, Bessaklia H, Lachapelle P. Strain differences in light-induced retinopathy. PLoS One. 2016; 11: e0158082.","DOI":"10.1371\/journal.pone.0158082"},{"key":"i1552-5783-59-7-2999-b87","doi-asserted-by":"crossref","unstructured":"Corbo JC, Myers CA, Lawrence KA, Jadhav AP, Cepko CL. A typology of photoreceptor gene expression patterns in the mouse. Proc Natl Acad Sci U S A. 2007; 104: 12069\u201312074.","DOI":"10.1073\/pnas.0705465104"},{"key":"i1552-5783-59-7-2999-b88","doi-asserted-by":"crossref","unstructured":"Fox DA, Rubinstein SD. Age-related changes in retinal sensitivity, rhodopsin content and rod outer segment length in hooded rats following low-level lead exposure during development. Exp Eye Res. 1989; 48: 237\u2013249.","DOI":"10.1016\/S0014-4835(89)80073-9"},{"key":"i1552-5783-59-7-2999-b89","unstructured":"Rapp LM, Fisher PL, Dhindsa HS. Reduced rate of rod outer segment disk synthesis in photoreceptor cells recovering from UVA light damage. Invest Ophthalmol Vis Sci. 1994; 35: 3540\u20133548."},{"key":"i1552-5783-59-7-2999-b90","doi-asserted-by":"crossref","unstructured":"Mao H, Seo SJ, Biswal MR, et al. Mitochondrial oxidative stress in the retinal pigment epithelium leads to localized retinal degeneration. Invest Ophthalmol Vis Sci. 2014; 55: 4613\u20134627.","DOI":"10.1167\/iovs.14-14633"},{"key":"i1552-5783-59-7-2999-b91","doi-asserted-by":"crossref","unstructured":"Rapp LM, Williams TP. The role of ocular pigmentation in protecting against retinal light damage. Vision Res. 1980; 20: 1127\u20131131.","DOI":"10.1016\/0042-6989(80)90050-4"},{"key":"i1552-5783-59-7-2999-b92","unstructured":"Yoshizawa K, Nambu H, Yang J, et al. Mechanisms of photoreceptor cell apoptosis induced by N-methyl-N-nitrosourea in Sprague-Dawley rats. Lab Invest. 1999; 79: 1359\u20131367."},{"key":"i1552-5783-59-7-2999-b93","doi-asserted-by":"crossref","unstructured":"LaVail MM, Matthes MT, Yasumura D, Steinberg RH. Variability in rate of cone degeneration in the retinal degeneration (rd\/rd) mouse. Exp Eye Res. 1997; 65: 45\u201350.","DOI":"10.1006\/exer.1997.0308"},{"key":"i1552-5783-59-7-2999-b94","doi-asserted-by":"crossref","unstructured":"Maeda A, Maeda T, Golczak M, Palczewski K. Retinopathy in mice induced by disrupted all-trans-retinal clearance. J Biol Chem. 2008; 283: 26684\u201326693.","DOI":"10.1074\/jbc.M804505200"},{"key":"i1552-5783-59-7-2999-b95","doi-asserted-by":"crossref","unstructured":"Smit-McBride Z, Oltjen SL, Lavail MM, Hjelmeland LM. A strong genetic determinant of hyperoxia-related retinal degeneration on mouse chromosome 6. Invest Ophthalmol Vis Sci. 2007; 48: 405\u2013411.","DOI":"10.1167\/iovs.06-0854"},{"key":"i1552-5783-59-7-2999-b96","doi-asserted-by":"crossref","unstructured":"Liang L, Katagiri Y, Franco LM, et al. Long-term cellular and regional specificity of the photoreceptor toxin, iodoacetic acid (IAA), in the rabbit retina. Vis Neurosci. 2008; 25: 167\u2013177.","DOI":"10.1017\/S0952523808080401"},{"key":"i1552-5783-59-7-2999-b97","doi-asserted-by":"crossref","unstructured":"Polosa A, Liu W, Lachapelle P. Retinotopic distribution of structural and functional damages following bright light exposure of juvenile rats. PLoS One. 2016; 11: e0146979.","DOI":"10.1371\/journal.pone.0146979"},{"key":"i1552-5783-59-7-2999-b98","doi-asserted-by":"crossref","unstructured":"Stone J, Maslim J, Valter-Kocsi K, et al. Mechanisms of photoreceptor death and survival in mammalian retina. Prog Retin Eye Res. 1999; 18: 689\u2013735.","DOI":"10.1016\/S1350-9462(98)00032-9"},{"key":"i1552-5783-59-7-2999-b99","doi-asserted-by":"crossref","unstructured":"Organisciak DT, Vaughan DK. Retinal light damage: mechanisms and protection. Prog Retin Eye Res. 2010; 29: 113\u2013134.","DOI":"10.1016\/j.preteyeres.2009.11.004"},{"key":"i1552-5783-59-7-2999-b100","doi-asserted-by":"crossref","unstructured":"Tushev G, Schuman EM. Rethinking functional segregation: gradients of gene expression in area CA1. Neuron. 2016; 89: 242\u2013243.","DOI":"10.1016\/j.neuron.2016.01.002"},{"key":"i1552-5783-59-7-2999-b101","doi-asserted-by":"crossref","unstructured":"Velez G, Machlab DA, Tang PH, et al. Proteomic analysis of the human retina reveals region-specific susceptibilities to metabolic- and oxidative stress-related diseases. PLoS One. 2018; 13: e0193250.","DOI":"10.1371\/journal.pone.0193250"},{"key":"i1552-5783-59-7-2999-b102","doi-asserted-by":"crossref","unstructured":"Patel AK, Davis A, Rodriguez ME, Agron S, Hackam AS. Protective effects of a grape-supplemented diet in a mouse model of retinal degeneration. Nutrition. 2016; 32: 384\u2013390.","DOI":"10.1016\/j.nut.2015.09.017"},{"key":"i1552-5783-59-7-2999-b103","doi-asserted-by":"crossref","unstructured":"Lederman M, Hagbi-Levi S, Grunin M, et al. Degeneration modulates retinal response to transient exogenous oxidative injury. PLoS One. 2014; 9: e87751.","DOI":"10.1371\/journal.pone.0087751"},{"key":"i1552-5783-59-7-2999-b104","doi-asserted-by":"crossref","unstructured":"Chen H, Liu B, Lukas TJ, Suyeoka G, Wu G, Neufeld AH. Changes in iron regulatory proteins in the aged rodent neural retina. Neurobiol Aging. 2009; 30: 1865\u20131876.","DOI":"10.1016\/j.neurobiolaging.2008.01.002"},{"key":"i1552-5783-59-7-2999-b105","doi-asserted-by":"crossref","unstructured":"Muralidharan P, Cserne Szappanos H, Ingley E, Hool L. Evidence for redox sensing by a human cardiac calcium channel. Sci Rep. 2016; 6: 19067.","DOI":"10.1038\/srep19067"},{"key":"i1552-5783-59-7-2999-b106","doi-asserted-by":"crossref","unstructured":"Ko EA, Wan J, Yamamura A, et al. Functional characterization of voltage-dependent Ca2+ channels in mouse pulmonary arterial smooth muscle cells: divergent effect of ROS. Am J Physiol Cell Physiol. 2013; 304: C1042\u2013C1052.","DOI":"10.1152\/ajpcell.00304.2012"},{"key":"i1552-5783-59-7-2999-b107","doi-asserted-by":"crossref","unstructured":"Chaplin NL, Nieves-Cintron M, Fresquez AM, Navedo MF, Amberg GC. Arterial smooth muscle mitochondria amplify hydrogen peroxide microdomains functionally coupled to L-type calcium channels. Circ Res. 2015; 117: 1013\u20131023.","DOI":"10.1161\/CIRCRESAHA.115.306996"},{"key":"i1552-5783-59-7-2999-b108","doi-asserted-by":"crossref","unstructured":"Yang L, Xu J, Minobe E, et al. Mechanisms underlying the modulation of L-type Ca2+ channel by hydrogen peroxide in guinea pig ventricular myocytes. J Physiol Sci. 2013; 63: 419\u2013426.","DOI":"10.1007\/s12576-013-0279-2"},{"key":"i1552-5783-59-7-2999-b109","doi-asserted-by":"crossref","unstructured":"Le\u00f3n OS, Men\u00e9ndez S, Merino N, et al. Ozone oxidative preconditioning: a protection against cellular damage by free radicals. Mediators Inflamm. 1998; 7: 289\u2013294.","DOI":"10.1080\/09629359890983"},{"key":"i1552-5783-59-7-2999-b110","doi-asserted-by":"crossref","unstructured":"Chen J, Wang Q, Zhang H, et al. In vivo quantification of T1, T2, and apparent diffusion coefficient in the mouse retina at 11.74T. Magn Reson Med. 2008; 59: 731\u2013738.","DOI":"10.1002\/mrm.21570"},{"key":"i1552-5783-59-7-2999-b111","doi-asserted-by":"crossref","unstructured":"Berkowitz BA, Schmidt T, Podolsky RH, Roberts R. Melanopsin phototransduction contributes to light-evoked choroidal expansion and rod L-type calcium channel function in vivo. Invest Ophthalmol Vis Sci. 2016; 57: 5314\u20135319.","DOI":"10.1167\/iovs.16-20186"},{"key":"i1552-5783-59-7-2999-b112","doi-asserted-by":"crossref","unstructured":"Ferguson LR, Dominguez JM II, Balaiya S, Grover S, Chalam KV. Retinal thickness normative data in wild-type mice using customized miniature SD-OCT. PLoS One. 2013; 8: e67265.","DOI":"10.1371\/journal.pone.0067265"}],"container-title":["Investigative Opthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?articleid=2684839","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:30:54Z","timestamp":1791927054000},"score":1,"resource":{"primary":{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.18-23829"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,11]]},"references-count":112,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,6,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.18-23829","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2018,6,11]]}}}