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Published in: Documenta Ophthalmologica 3/2009

01-12-2009 | Original Research Article

Dimethyl sulphoxide dose–response on rat retinal function

Authors: Tina I. Tsai, Bang V. Bui, Algis J. Vingrys

Published in: Documenta Ophthalmologica | Issue 3/2009

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Abstract

The aim of the study is to determine whether dimethyl sulphoxide (DMSO), a common laboratory solvent, impacts retinal function. Long Evans rats (n = 17) were intravitreally injected with five different doses of DMSO representative of those reported in the literature and spanning over 3 log units of vitreal concentration (0.01–8%). Retinal function was evaluated 1 h after injection using electroretinograms, and the waveform was decomposed into outer (photoreceptor), middle (ON-bipolar cell) and inner retinal (amacrine and ganglion cell) components. DMSO induces a dose-dependent decrease in retinal function for concentrations of 0.6% or more which is retinal layer specific. The photoreceptors of the outer retina returned normal responses at all doses (P > 0.05), whereas the mid-retinal bipolar cell response showed dose-dependent losses ranging from 21 ± 1 to 82 ± 1% (0.6–8% DMSO; P < 0.05). In a similar dose-dependent fashion, the inner retinal response was also affected by DMSO (0.6–8%: 23 ± 12 to 98 ± 3% loss, P < 0.05). A single dose of DMSO ≤0.1% (2.96 × 10−5 μM) may be safely used to dilute compounds injected into the vitreous of a rat eye. Higher doses produce short-term (at least 24 h) retinal dysfunction.
Literature
1.
go back to reference Silverman C (1983) Ocular toxicity of experimental intravitreal DMSO. J Toxicol Cutaneous Ocul Toxicol 2(2–3):193 Silverman C (1983) Ocular toxicity of experimental intravitreal DMSO. J Toxicol Cutaneous Ocul Toxicol 2(2–3):193
2.
go back to reference Yoshizumi MO, Banihashemi AR (1988) Experimental intravitreal ketoconazole in DMSO. Retina 8(3):210–215CrossRefPubMed Yoshizumi MO, Banihashemi AR (1988) Experimental intravitreal ketoconazole in DMSO. Retina 8(3):210–215CrossRefPubMed
3.
go back to reference Schulman JA, Peyman GA, Dietlein J, Fiscella R, Colantino B (1989) Ocular toxicity after intravitreal injection of terconazole. Ann Ophthalmol 21(9):345–347PubMed Schulman JA, Peyman GA, Dietlein J, Fiscella R, Colantino B (1989) Ocular toxicity after intravitreal injection of terconazole. Ann Ophthalmol 21(9):345–347PubMed
4.
go back to reference Daniels SA, Coonley KG, Yoshizumi MO (1990) Taxol treatment of experimental proliferative vitreoretinopathy. Graefes Arch Clin Exp Ophthalmol 228(6):513–516CrossRefPubMed Daniels SA, Coonley KG, Yoshizumi MO (1990) Taxol treatment of experimental proliferative vitreoretinopathy. Graefes Arch Clin Exp Ophthalmol 228(6):513–516CrossRefPubMed
5.
go back to reference Schulman JA, Peyman GA, Dietlein J, Fiscella R (1991) Ocular toxicity of experimental intravitreal itraconazole. Int Ophthalmol 15(1):21–24CrossRefPubMed Schulman JA, Peyman GA, Dietlein J, Fiscella R (1991) Ocular toxicity of experimental intravitreal itraconazole. Int Ophthalmol 15(1):21–24CrossRefPubMed
6.
go back to reference Negishi K, Stell WK, Teranishi T, Karkhanis A, Owusu-Yaw V, Takasaki Y (1991) Induction of proliferating cell nuclear antigen (PCNA)-immunoreactive cells in goldfish retina following intravitreal injection with 6-hydroxydopamine. Cell Mol Neurobiol 11(6):639–659CrossRefPubMed Negishi K, Stell WK, Teranishi T, Karkhanis A, Owusu-Yaw V, Takasaki Y (1991) Induction of proliferating cell nuclear antigen (PCNA)-immunoreactive cells in goldfish retina following intravitreal injection with 6-hydroxydopamine. Cell Mol Neurobiol 11(6):639–659CrossRefPubMed
7.
go back to reference Li B, Yang C, Rosenbaum DM, Roth S (2000) Signal transduction mechanisms involved in ischemic preconditioning in the rat retina in vivo. Exp Eye Res 70(6):755–765CrossRefPubMed Li B, Yang C, Rosenbaum DM, Roth S (2000) Signal transduction mechanisms involved in ischemic preconditioning in the rat retina in vivo. Exp Eye Res 70(6):755–765CrossRefPubMed
8.
go back to reference Perche O, Doly M, Ranchon-Cole I (2007) Caspase-dependent apoptosis in light-induced retinal degeneration. Invest Ophthalmol Vis Sci 48(6):2753–2759CrossRefPubMed Perche O, Doly M, Ranchon-Cole I (2007) Caspase-dependent apoptosis in light-induced retinal degeneration. Invest Ophthalmol Vis Sci 48(6):2753–2759CrossRefPubMed
9.
go back to reference Rubin LF (1975) Toxicity of dimethyl sulfoxide, alone and in combination. Ann N Y Acad Sci 243:98–103CrossRefPubMed Rubin LF (1975) Toxicity of dimethyl sulfoxide, alone and in combination. Ann N Y Acad Sci 243:98–103CrossRefPubMed
10.
go back to reference Brayton CF (1986) Dimethyl sulfoxide (DMSO): a review. Cornell Vet 76(1):61–90PubMed Brayton CF (1986) Dimethyl sulfoxide (DMSO): a review. Cornell Vet 76(1):61–90PubMed
11.
go back to reference Santos NC, Figueira-Coelho J, Martins-Silva J, Saldanha C (2003) Multidisciplinary utilization of dimethyl sulfoxide: pharmacological, cellular, and molecular aspects. Biochem Pharmacol 65(7):1035–1041CrossRefPubMed Santos NC, Figueira-Coelho J, Martins-Silva J, Saldanha C (2003) Multidisciplinary utilization of dimethyl sulfoxide: pharmacological, cellular, and molecular aspects. Biochem Pharmacol 65(7):1035–1041CrossRefPubMed
12.
go back to reference Colucci M, Maione F, Bonito MC, Piscopo A, Di Giannuario A, Pieretti S (2008) New insights of dimethyl sulphoxide effects (DMSO) on experimental in vivo models of nociception and inflammation. Pharmacol Res 57(6):419–425CrossRefPubMed Colucci M, Maione F, Bonito MC, Piscopo A, Di Giannuario A, Pieretti S (2008) New insights of dimethyl sulphoxide effects (DMSO) on experimental in vivo models of nociception and inflammation. Pharmacol Res 57(6):419–425CrossRefPubMed
13.
go back to reference Farkas E, Annahazi A, Institoris A, Mihaly A, Luiten PG, Bari F (2005) Diazoxide and dimethyl sulphoxide alleviate experimental cerebral hypoperfusion-induced white matter injury in the rat brain. Neurosci Lett 373(3):195–199CrossRefPubMed Farkas E, Annahazi A, Institoris A, Mihaly A, Luiten PG, Bari F (2005) Diazoxide and dimethyl sulphoxide alleviate experimental cerebral hypoperfusion-induced white matter injury in the rat brain. Neurosci Lett 373(3):195–199CrossRefPubMed
14.
go back to reference Kishioka T, Iida C, Fujii K, Nagae R, Onishi Y, Ichi I, Kojo S (2007) Effect of dimethyl sulphoxide on oxidative stress, activation of mitogen activated protein kinase and necrosis caused by thioacetamide in the rat liver. Eur J Pharmacol 564(1–3):190–195CrossRefPubMed Kishioka T, Iida C, Fujii K, Nagae R, Onishi Y, Ichi I, Kojo S (2007) Effect of dimethyl sulphoxide on oxidative stress, activation of mitogen activated protein kinase and necrosis caused by thioacetamide in the rat liver. Eur J Pharmacol 564(1–3):190–195CrossRefPubMed
15.
go back to reference Lin CK, Kalunta CI, Chen FS, Nguyen TT, Kaptein JS, Lad PM (1995) Dimethyl sulfoxide suppresses apoptosis in Burkitt’s lymphoma cells. Exp Cell Res 216(2):403–410CrossRefPubMed Lin CK, Kalunta CI, Chen FS, Nguyen TT, Kaptein JS, Lad PM (1995) Dimethyl sulfoxide suppresses apoptosis in Burkitt’s lymphoma cells. Exp Cell Res 216(2):403–410CrossRefPubMed
16.
go back to reference Liu J, Yoshikawa H, Nakajima Y, Tasaka K (2001) Involvement of mitochondrial permeability transition and caspase-9 activation in dimethyl sulfoxide-induced apoptosis of EL-4 lymphoma cells. Int Immunopharmacol 1(1):63–74CrossRefPubMed Liu J, Yoshikawa H, Nakajima Y, Tasaka K (2001) Involvement of mitochondrial permeability transition and caspase-9 activation in dimethyl sulfoxide-induced apoptosis of EL-4 lymphoma cells. Int Immunopharmacol 1(1):63–74CrossRefPubMed
17.
go back to reference Qi W, Ding D, Salvi RJ (2008) Cytotoxic effects of dimethyl sulphoxide (DMSO) on cochlear organotypic cultures. Hear Res 236(1–2):52–60CrossRefPubMed Qi W, Ding D, Salvi RJ (2008) Cytotoxic effects of dimethyl sulphoxide (DMSO) on cochlear organotypic cultures. Hear Res 236(1–2):52–60CrossRefPubMed
18.
go back to reference Gordon DM (1967) Dimethyl sulfoxide in ophthalmology, with especial reference to possible toxic effects. Ann N Y Acad Sci 141(1):392–401CrossRefPubMed Gordon DM (1967) Dimethyl sulfoxide in ophthalmology, with especial reference to possible toxic effects. Ann N Y Acad Sci 141(1):392–401CrossRefPubMed
19.
go back to reference Hanna C, Fraunfelder FT, Meyer SM (1977) Effects of dimethyl sulfoxide on ocular inflammation. Ann Ophthalmol 9(1):61–65PubMed Hanna C, Fraunfelder FT, Meyer SM (1977) Effects of dimethyl sulfoxide on ocular inflammation. Ann Ophthalmol 9(1):61–65PubMed
20.
go back to reference Lu C, Mattson MP (2001) Dimethyl sulfoxide suppresses NMDA- and AMPA-induced ion currents and calcium influx and protects against excitotoxic death in hippocampal neurons. Exp Neurol 170(1):180–185CrossRefPubMed Lu C, Mattson MP (2001) Dimethyl sulfoxide suppresses NMDA- and AMPA-induced ion currents and calcium influx and protects against excitotoxic death in hippocampal neurons. Exp Neurol 170(1):180–185CrossRefPubMed
21.
go back to reference Aita K, Irie H, Tanuma Y, Toida S, Okuma Y, Mori S, Shiga J (2005) Apoptosis in murine lymphoid organs following intraperitoneal administration of dimethyl sulfoxide (DMSO). Exp Mol Pathol 79(3):265–271CrossRefPubMed Aita K, Irie H, Tanuma Y, Toida S, Okuma Y, Mori S, Shiga J (2005) Apoptosis in murine lymphoid organs following intraperitoneal administration of dimethyl sulfoxide (DMSO). Exp Mol Pathol 79(3):265–271CrossRefPubMed
22.
go back to reference Noel PR, Barnett KC, Davies RE, Jolly DW, Leahy JS, Mawdesley-Thomas LE, Shillam KW, Squires PF, Street AE, Tucker WC, Worden AN (1975) The toxicity of dimethyl sulphoxide (DMSO) for the dog, pig, rat and rabbit. Toxicology 3(2):143–169CrossRefPubMed Noel PR, Barnett KC, Davies RE, Jolly DW, Leahy JS, Mawdesley-Thomas LE, Shillam KW, Squires PF, Street AE, Tucker WC, Worden AN (1975) The toxicity of dimethyl sulphoxide (DMSO) for the dog, pig, rat and rabbit. Toxicology 3(2):143–169CrossRefPubMed
23.
go back to reference Westbrook AM, Crewther SG, Liang H, Beresford JA, Allen M, Keller I, Crewther DP (1995) Formoguanamine-induced inhibition of deprivation myopia in chick is accompanied by choroidal thinning while retinal function is retained. Vision Res 35(14):2075–2088CrossRefPubMed Westbrook AM, Crewther SG, Liang H, Beresford JA, Allen M, Keller I, Crewther DP (1995) Formoguanamine-induced inhibition of deprivation myopia in chick is accompanied by choroidal thinning while retinal function is retained. Vision Res 35(14):2075–2088CrossRefPubMed
24.
go back to reference Zhang X, Jones D, Gonzalez-Lima F (2002) Mouse model of optic neuropathy caused by mitochondrial complex I dysfunction. Neurosci Lett 326(2):97–100CrossRefPubMed Zhang X, Jones D, Gonzalez-Lima F (2002) Mouse model of optic neuropathy caused by mitochondrial complex I dysfunction. Neurosci Lett 326(2):97–100CrossRefPubMed
25.
go back to reference Weymouth AE, Vingrys AJ (2008) Rodent electroretinography: methods for extraction and interpretation of rod and cone responses. Prog Retin Eye Res 27(1):1–44CrossRefPubMed Weymouth AE, Vingrys AJ (2008) Rodent electroretinography: methods for extraction and interpretation of rod and cone responses. Prog Retin Eye Res 27(1):1–44CrossRefPubMed
26.
go back to reference Berkowitz BA, Roberts R, Goebel DJ, Luan H (2006) Noninvasive and simultaneous imaging of layer-specific retinal functional adaptation by manganese-enhanced MRI. Invest Ophthalmol Vis Sci 47(6):2668–2674CrossRefPubMed Berkowitz BA, Roberts R, Goebel DJ, Luan H (2006) Noninvasive and simultaneous imaging of layer-specific retinal functional adaptation by manganese-enhanced MRI. Invest Ophthalmol Vis Sci 47(6):2668–2674CrossRefPubMed
27.
go back to reference Bui BV, Fortune B (2004) Ganglion cell contributions to the rat full-field electroretinogram. J Physiol 555(Pt 1):153–173PubMed Bui BV, Fortune B (2004) Ganglion cell contributions to the rat full-field electroretinogram. J Physiol 555(Pt 1):153–173PubMed
29.
go back to reference Cordeiro MF, Guo L, Luong V, Harding G, Wang W, Jones HE, Moss SE, Sillito AM, Fitzke FW (2004) Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration. Proc Natl Acad Sci USA 101(36):13352–13356CrossRefPubMed Cordeiro MF, Guo L, Luong V, Harding G, Wang W, Jones HE, Moss SE, Sillito AM, Fitzke FW (2004) Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration. Proc Natl Acad Sci USA 101(36):13352–13356CrossRefPubMed
30.
go back to reference Guo L, Salt TE, Maass A, Luong V, Moss SE, Fitzke FW, Cordeiro MF (2006) Assessment of neuroprotective effects of glutamate modulation on glaucoma-related retinal ganglion cell apoptosis in vivo. Invest Ophthalmol Vis Sci 47(2):626–633CrossRefPubMed Guo L, Salt TE, Maass A, Luong V, Moss SE, Fitzke FW, Cordeiro MF (2006) Assessment of neuroprotective effects of glutamate modulation on glaucoma-related retinal ganglion cell apoptosis in vivo. Invest Ophthalmol Vis Sci 47(2):626–633CrossRefPubMed
31.
go back to reference He Z, Bui BV, Vingrys AJ (2006) The rate of functional recovery from acute IOP elevation. Invest Ophthalmol Vis Sci 47(11):4872–4880CrossRefPubMed He Z, Bui BV, Vingrys AJ (2006) The rate of functional recovery from acute IOP elevation. Invest Ophthalmol Vis Sci 47(11):4872–4880CrossRefPubMed
32.
go back to reference Marmor MF, Fulton AB, Holder GE, Miyake Y, Brigell M, Bach M (2009) ISCEV standard for full-field clinical electroretinography (2008 update). Doc Ophthalmol 118(1):69–77CrossRefPubMed Marmor MF, Fulton AB, Holder GE, Miyake Y, Brigell M, Bach M (2009) ISCEV standard for full-field clinical electroretinography (2008 update). Doc Ophthalmol 118(1):69–77CrossRefPubMed
33.
go back to reference Hood DC, Birch DG (1990) The A-wave of the human electroretinogram and rod receptor function. Invest Ophthalmol Vis Sci 31(10):2070–2081PubMed Hood DC, Birch DG (1990) The A-wave of the human electroretinogram and rod receptor function. Invest Ophthalmol Vis Sci 31(10):2070–2081PubMed
34.
go back to reference Hood DC, Birch DG (1993) Light adaptation of human rod receptors: the leading edge of the human a-wave and models of rod receptor activity. Vision Res 33(12):1605–1618CrossRefPubMed Hood DC, Birch DG (1993) Light adaptation of human rod receptors: the leading edge of the human a-wave and models of rod receptor activity. Vision Res 33(12):1605–1618CrossRefPubMed
35.
go back to reference Robson JG, Saszik SM, Ahmed J, Frishman LJ (2003) Rod and cone contributions to the a-wave of the electroretinogram of the macaque. J Physiol 547(Pt 2):509–530CrossRefPubMed Robson JG, Saszik SM, Ahmed J, Frishman LJ (2003) Rod and cone contributions to the a-wave of the electroretinogram of the macaque. J Physiol 547(Pt 2):509–530CrossRefPubMed
36.
go back to reference Hood DC, Birch DG (1992) A computational model of the amplitude and implicit time of the b-wave of the human ERG. Vis Neurosci 8(2):107–126CrossRefPubMed Hood DC, Birch DG (1992) A computational model of the amplitude and implicit time of the b-wave of the human ERG. Vis Neurosci 8(2):107–126CrossRefPubMed
37.
go back to reference Fulton AB, Rushton WA (1978) The human rod ERG: correlation with psychophysical responses in light and dark adaptation. Vision Res 18(7):793–800CrossRefPubMed Fulton AB, Rushton WA (1978) The human rod ERG: correlation with psychophysical responses in light and dark adaptation. Vision Res 18(7):793–800CrossRefPubMed
38.
go back to reference Robson JG, Frishman LJ (1996) Photoreceptor and bipolar cell contributions to the cat electroretinogram: a kinetic model for the early part of the flash response. J Opt Soc Am A Opt Image Sci Vis 13(3):613–622CrossRefPubMed Robson JG, Frishman LJ (1996) Photoreceptor and bipolar cell contributions to the cat electroretinogram: a kinetic model for the early part of the flash response. J Opt Soc Am A Opt Image Sci Vis 13(3):613–622CrossRefPubMed
39.
go back to reference Severns ML, Johnson MA (1993) Predicting outcome in central retinal vein occlusion using the flicker electroretinogram. Arch Ophthalmol 111(8):1123–1130PubMed Severns ML, Johnson MA (1993) Predicting outcome in central retinal vein occlusion using the flicker electroretinogram. Arch Ophthalmol 111(8):1123–1130PubMed
40.
go back to reference Saszik SM, Robson JG, Frishman LJ (2002) The scotopic threshold response of the dark-adapted electroretinogram of the mouse. J Physiol 543(Pt 3):899–916CrossRefPubMed Saszik SM, Robson JG, Frishman LJ (2002) The scotopic threshold response of the dark-adapted electroretinogram of the mouse. J Physiol 543(Pt 3):899–916CrossRefPubMed
41.
go back to reference Fortune B, Bui BV, Morrison JC, Johnson EC, Dong J, Cepurna WO, Jia L, Barber S, Cioffi GA (2004) Selective ganglion cell functional loss in rats with experimental glaucoma. Invest Ophthalmol Vis Sci 45(6):1854–1862CrossRefPubMed Fortune B, Bui BV, Morrison JC, Johnson EC, Dong J, Cepurna WO, Jia L, Barber S, Cioffi GA (2004) Selective ganglion cell functional loss in rats with experimental glaucoma. Invest Ophthalmol Vis Sci 45(6):1854–1862CrossRefPubMed
42.
go back to reference Stockton RA, Slaughter MM (1989) B-wave of the electroretinogram. A reflection of ON bipolar cell activity. J Gen Physiol 93(1):101–122CrossRefPubMed Stockton RA, Slaughter MM (1989) B-wave of the electroretinogram. A reflection of ON bipolar cell activity. J Gen Physiol 93(1):101–122CrossRefPubMed
43.
go back to reference Gurevich L, Slaughter MM (1993) Comparison of the waveforms of the ON bipolar neuron and the b-wave of the electroretinogram. Vision Res 33(17):2431–2435CrossRefPubMed Gurevich L, Slaughter MM (1993) Comparison of the waveforms of the ON bipolar neuron and the b-wave of the electroretinogram. Vision Res 33(17):2431–2435CrossRefPubMed
44.
go back to reference Borchard U (1975) The effect of dimethylsulfoxide (DMSO) on the bioelectric activity of the isolated retina. Pflugers Arch 355(Suppl.):222 Borchard U (1975) The effect of dimethylsulfoxide (DMSO) on the bioelectric activity of the isolated retina. Pflugers Arch 355(Suppl.):222
45.
go back to reference Tsvyetlynska NA, Hill RH, Grillner S (2005) Role of AMPA receptor desensitization and the side effects of a DMSO vehicle on reticulospinal EPSPs and locomotor activity. J Neurophysiol 94(6):3951–3960CrossRefPubMed Tsvyetlynska NA, Hill RH, Grillner S (2005) Role of AMPA receptor desensitization and the side effects of a DMSO vehicle on reticulospinal EPSPs and locomotor activity. J Neurophysiol 94(6):3951–3960CrossRefPubMed
46.
go back to reference Nakahiro M, Arakawa O, Narahashi T, Ukai S, Kato Y, Nishinuma K, Nishimura T (1992) Dimethyl sulfoxide (DMSO) blocks GABA-induced current in rat dorsal root ganglion neurons. Neurosci Lett 138(1):5–8CrossRefPubMed Nakahiro M, Arakawa O, Narahashi T, Ukai S, Kato Y, Nishinuma K, Nishimura T (1992) Dimethyl sulfoxide (DMSO) blocks GABA-induced current in rat dorsal root ganglion neurons. Neurosci Lett 138(1):5–8CrossRefPubMed
47.
go back to reference Sawada M, Sato M (1975) The effect of dimethyl sulfoxide on the neuronal excitability and cholinergic transmission in Aplysia ganglion cells. Ann N Y Acad Sci 243:337–357CrossRefPubMed Sawada M, Sato M (1975) The effect of dimethyl sulfoxide on the neuronal excitability and cholinergic transmission in Aplysia ganglion cells. Ann N Y Acad Sci 243:337–357CrossRefPubMed
Metadata
Title
Dimethyl sulphoxide dose–response on rat retinal function
Authors
Tina I. Tsai
Bang V. Bui
Algis J. Vingrys
Publication date
01-12-2009
Publisher
Springer-Verlag
Published in
Documenta Ophthalmologica / Issue 3/2009
Print ISSN: 0012-4486
Electronic ISSN: 1573-2622
DOI
https://doi.org/10.1007/s10633-009-9191-8

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