Photobiomodulation therapy in ophthalmology
Keywords:photobiomodulation therapy, far-red to near-infrared light spectrum, retina, mitochondria
Photobiomodulation (PBM) therapy is a form of light therapy that utilizes non-ionizing forms of light sources in the far-red to near-infrared spectrum to produce non-thermal photochemical reactions in different biological structures. The paper reviews the experience of implementing (a) PBM in different fields of medicine (e.g., ophthalmology) and (b) the known mechanisms of PBM-induced effects on cells and tissues.
Anders JJ, Lanzafame RJ, Arany PR. Low-level light/laser therapy versus photobiomodulation therapy. Photomed Laser Surg. 2015;33(4):183-184.
Karu TI. Effects of visible radiation on cultured cells. Photochem Photobiol. 1990;52(6):1089-1098.
Geneva II. Photobiomodulation for the treatment of retinal diseases: a review. Int J Ophthalmol. 2016;9(1):145-152.
Mester E, Szende B, G?rtner P. Die Wirkung der Lasstrahlen auf den Haarwuchs der Maus [The effect of laser beams on the growth of hair in mice]. Radiobiol Radiother (Berl). 1968;9(5):621-626.
Kov?cs IB, Mester E, G?r?g P. Stimulation of wound healing with laser beam in the rat. Experientia. 1974;30(11):1275-1276.
Linnik LA, Usov NI, Chechin PP, Pelepchuk OS. Perspektivy ispol'zovaniia stimuliruiushche? lazerno? terapii v oftal'mologii [Prospects for using stimulating laser therapy in ophthalmology]. Oftalmol Zh. 1982;37(4):193-7. Russian.
Linnik LA. Lazernaia terapiia v oftal'mologii [Laser therapy in ophthalmology]. Oftalmol Zh. 1985;(8):451-5.
Karu T, Pyatibrat L, Kalendo G. Irradiation with He-Ne laser increases ATP level in cells cultivated in vitro. J Photochem Photobiol B. 1995;27(3):219-223.
Manteifel V, Bakeeva L, Karu T. Ultrastructural changes in chondriome of human lymphocytes after irradiation with He-Ne laser: appearance of giant mitochondria. J Photochem Photobiol B. 1997;38(1):25-30.
Sutherland JC. Biological effects of polychromatic light. Photochem Photobiol. 2002;76(2):164-170.
Kato M, Shinizawa K, Yoshikawa S. Cythochrome oxidase is a possible photoreceptor in mitochondria. Photobiochem Photobiophys. 1981;2:263–269
Greco M, Guida G, Perlino E, Marra E, Quagliariello E. Increase in RNA and protein synthesis by mitochondria irradiated with helium-neon laser. Biochem Biophys Res Commun. 1989;163(3):1428-1434.
Karu T. Primary and secondary mechanisms of action of visible to near-IR radiation on cells. J Photochem Photobiol B. 1999;49(1):1-17.
Passarella S, Casamassima E, Molinari S, et al. Increase of proton electrochemical potential and ATP synthesis in rat liver mitochondria irradiated in vitro by helium-neon laser. FEBS Lett. 1984;175(1):95-99.
Karu TI, Kolyakov SF. Exact action spectra for cellular responses relevant to phototherapy. Photomed Laser Surg. 2005;23(4):355-361.
Hawkins D, Abrahamse H. Biological effects of helium-neon laser irradiation on normal and wounded human skin fibroblasts. Photomed Laser Surg. 2005;23(3):251-259.
Chung H, Dai T, Sharma SK, Huang YY, Carroll JD, Hamblin MR. The nuts and bolts of low-level laser (light) therapy. Ann Biomed Eng. 2012;40(2):516-533.
Capaldi RA, Malatesta F, Darley-Usmar VM. Structure of cytochrome c oxidase. Biochim Biophys Acta. 1983;726(2):135-148.
Quirk BJ, Whelan HT. What Lies at the Heart of Photobiomodulation: Light, Cytochrome C Oxidase, and Nitric Oxide - Review of the Evidence. Photobiomodulation, Photomedicine, and Laser Surgery. 2020;38(9);527-530.
Karu TI, Pyatibrat LV, Kolyakov SF, Afanasyeva NI. Absorption measurements of a cell monolayer relevant to phototherapy: reduction of cytochrome c oxidase under near IR radiation. J Photochem Photobiol B. 2005;81(2):98-106.
Wong-Riley MT, Liang HL, Eells JT, et al. Photobiomodulation directly benefits primary neurons functionally inactivated by toxins: role of cytochrome c oxidase. J Biol Chem. 2005;280(6):4761-4771.
Karu TI, Pyatibrat LV, Afanasyeva NI. A novel mitochondrial signaling pathway activated by visible-to-near infrared radiation. Photochem Photobiol. 2004;80(2):366-372.
Lovschall H, Arenholt-Bindslev D. Low level laser therapy effect on mitochondrial rhodamine 123 uptake in human oral fibroblasts in vitro. Lasers Life Sci. 1998;8:101–116
Moore P, Ridgway TD, Higbee RG, Howard EW, Lucroy MD. Effect of wavelength on low-intensity laser irradiation-stimulated cell proliferation in vitro. Lasers Surg Med. 2005;36(1):8-12.
Hawkins D, Houreld N, Abrahamse H. Low level laser therapy (LLLT) as an effective therapeutic modality for delayed wound healing. Ann N Y Acad Sci. 2005;1056:486-493.
Yu HS, Wu CS, Yu CL, Kao YH, Chiou MH. Helium-neon laser irradiation stimulates migration and proliferation in melanocytes and induces repigmentation in segmental-type vitiligo. J Invest Dermatol. 2003;120(1):56-64.
Lohr NL, Keszler A, Pratt P, Bienengraber M, Warltier DC, Hogg N. Enhancement of nitric oxide release from nitrosyl hemoglobin and nitrosyl myoglobin by red/near infrared radiation: potential role in cardioprotection. J Mol Cell Cardiol. 2009;47(2):256-263.
Shiva S, Gladwin MT. Shining a light on tissue NO stores: near infrared release of NO from nitrite and nitrosylated hemes. J Mol Cell Cardiol. 2009;46(1):1-3.
Antunes F, Boveris A, Cadenas E. On the mechanism and biology of cytochrome oxidase inhibition by nitric oxide. Proc Natl Acad Sci U S A. 2004;101(48):16774-16779.
Mitchell UH, Mack GL. Low-level laser treatment with near-infrared light increases venous nitric oxide levels acutely: a single-blind, randomized clinical trial of efficacy. Am J Phys Med Rehabil. 2013;92(2):151-156.
Nawashiro H, Wada K, Nakai K, Sato S. Focal increase in cerebral blood flow after treatment with near-infrared light to the forehead in a patient in a persistent vegetative state. Photomed Laser Surg. 2012;30(4):231-233.
Liang HL, Whelan HT, Eells JT, Wong-Riley MT. Near-infrared light via light-emitting diode treatment is therapeutic against rotenone- and 1-methyl-4-phenylpyridinium ion-induced neurotoxicity. Neuroscience. 2008;153(4):963-974.
Ying R, Liang HL, Whelan HT, Eells JT, Wong-Riley MT. Pretreatment with near-infrared light via light-emitting diode provides added benefit against rotenone- and MPP+-induced neurotoxicity. Brain Res. 2008;1243:167-173.
Salehpour F, Farajdokht F, Cassano P, et al. Near-infrared photobiomodulation combined with coenzyme Q10 for depression in a mouse model of restraint stress: reduction in oxidative stress, neuroinflammation, and apoptosis. Brain Res Bull. 2019;144:213-222.
Wong-Riley MT. Energy metabolism of the visual system. Eye Brain. 2010;2:99-116.
Lock JH, Irani NK, Newman NJ. Neuro-ophthalmic manifestations of mitochondrial disorders and their management. Taiwan J Ophthalmol. 2020;11(1):39-52. Published 2020 Dec 4.
Albarracin R, Valter K. 670 nm red light preconditioning supports M?ller cell function: evidence from the white light-induced damage model in the rat retina. Photochem Photobiol. 2012;88(6):1418-1427.
Tang J, Du Y, Lee CA, Talahalli R, Eells JT, Kern TS. Low-intensity far-red light inhibits early lesions that contribute to diabetic retinopathy: in vivo and in vitro. Invest Ophthalmol Vis Sci. 2013;54(5):3681-3690.
Fuma S, Murase H, Kuse Y, Tsuruma K, Shimazawa M, Hara H. Photobiomodulation with 670 nm light increased phagocytosis in human retinal pigment epithelial cells. Mol Vis. 2015;21:883-892.
Karu TI. Mitochondrial signalling in mammalian cells activated by red and near-IR radiation. Photochem Photobiol. 2008;84(5):1091-1099.
Rojas JC, Gonzalez-Lima F. Low-level light therapy of the eye and brain. Eye Brain. 2011;3:49-67. Published 2011 Oct 14.
Peplow PV, Chung TY, Baxter GD. Laser photobiomodulation of wound healing: a review of experimental studies in mouse and rat animal models. Photomed Laser Surg. 2010;28(3):291-325.
Mester E, Nagylucskay S, Doklen A, Tisza S. Laser stimulation of wound healing. Acta Chir Acad Sci Hung. 1976;17:49–55
Thomas DW, O'Neill ID, Harding KG, Shepherd JP. Cutaneous wound healing: a current perspective. J Oral Maxillofac Surg. 1995;53(4):442-447.
Posten W, Wrone DA, Dover JS, Arndt KA, Silapunt S, Alam M. Low-level laser therapy for wound healing: mechanism and efficacy. Dermatol Surg. 2005;31(3):334-340.
Bisht D, Mehrotra R, Singh PA, Atri SC, Kumar A. Effect of helium-neon laser on wound healing. Indian J Exp Biol. 1999;37(2):187-189.
Meyers AD. Lasers and wound healing. Arch Otolaryngol Head Neck Surg. 1990;116:1128.
Skinner SM, Gage JP, Wilce PA, Shaw RM. A preliminary study of the effects of laser radiation on collagen metabolism in cell culture. Aust Dent J. 1996;41(3):188-192.
Bjordal JM, Coupp? C, Chow RT, Tun?r J, Ljunggren EA. A systematic review of low level laser therapy with location-specific doses for pain from chronic joint disorders. Aust J Physiother. 2003;49(2):107-116.
Wahl G, Bast?nier S. Der Softlaser in der postoperativen Nachsorge bei dentoalveol?ren Eingriffen [Soft laser in postoperative care in dentoalveolar treatment]. ZWR. 1991;100(8):512-515.
Chow RT, Johnson MI, Lopes-Martins RA, Bjordal JM. Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or active-treatment controlled trials. Lancet. 2009;374(9705):1897-1908.
Streeter J, De Taboada L, Oron U. Mechanisms of action of light therapy for stroke and acute myocardial infarction. Mitochondrion. 2004;4(5-6):569-576.
Oron U, Yaakobi T, Oron A, et al. Low-energy laser irradiation reduces formation of scar tissue after myocardial infarction in rats and dogs. Circulation. 2001;103(2):296-301.
Yaakobi T, Shoshany Y, Levkovitz S, Rubin O, Ben Haim SA, Oron U. Long-term effect of low energy laser irradiation on infarction and reperfusion injury in the rat heart. J Appl Physiol (1985). 2001;90(6):2411-2419.
Oron U, Yaakobi T, Oron A, et al. Attenuation of infarct size in rats and dogs after myocardial infarction by low-energy laser irradiation. Lasers Surg Med. 2001;28(3):204-211.
Lee G, Ikeda RM, Dwyer RM, Hussein H, Dietrich P, Mason DT. Feasibility of intravascular laser irradiation for in vivo visualization and therapy of cardiocirculatory diseases. Am Heart J. 1982;103(6):1076-1077.
Wong-Riley MT, Bai X, Buchmann E, Whelan HT. Light-emitting diode treatment reverses the effect of TTX on cytochrome oxidase in neurons. Neuroreport. 2001;12(14):3033-3037.
Hashmi JT, Huang YY, Osmani BZ, Sharma SK, Naeser MA, Hamblin MR. Role of low-level laser therapy in neurorehabilitation. PM R. 2010;2(12 Suppl 2):S292-S305.
Liang HL, Whelan HT, Eells JT, et al. Photobiomodulation partially rescues visual cortical neurons from cyanide-induced apoptosis. Neuroscience. 2006;139(2):639-649.
Naeser MA, Saltmarche A, Krengel MH, Hamblin MR, Knight JA. Improved cognitive function after transcranial, light-emitting diode treatments in chronic, traumatic brain injury: two case reports. Photomed Laser Surg. 2011;29(5):351-358.
Fitzgerald M, Hodgetts S, Van Den Heuvel C, et al. Red/near-infrared irradiation therapy for treatment of central nervous system injuries and disorders. Rev Neurosci. 2013;24(2):205-226.
Uozumi Y, Nawashiro H, Sato S, Kawauchi S, Shima K, Kikuchi M. Targeted increase in cerebral blood flow by transcranial near-infrared laser irradiation. Lasers Surg Med. 2010;42(6):566-576.
Rojas JC, Lee J, John JM, Gonzalez-Lima F. Neuroprotective effects of near-infrared light in an in vivo model of mitochondrial optic neuropathy. J Neurosci. 2008;28(50):13511-13521.
Lapchak PA, Salgado KF, Chao CH, Zivin JA. Transcranial near-infrared light therapy improves motor function following embolic strokes in rabbits: an extended therapeutic window study using continuous and pulse frequency delivery modes. Neuroscience. 2007;148(4):907-914.
Oron A, Oron U, Chen J, et al. Low-level laser therapy applied transcranially to rats after induction of stroke significantly reduces long-term neurological deficits. Stroke. 2006;37(10):2620-2624.
Detaboada L, Ilic S, Leichliter-Martha S, Oron U, Oron A, Streeter J. Transcranial application of low-energy laser irradiation improves neurological deficits in rats following acute stroke. Lasers Surg Med. 2006;38(1):70-73.
Lampl Y, Zivin JA, Fisher M, et al. Infrared laser therapy for ischemic stroke: a new treatment strategy: results of the NeuroThera Effectiveness and Safety Trial-1 (NEST-1). Stroke. 2007;38(6):1843-1849.
Moges H, Vasconcelos OM, Campbell WW, et al. Light therapy and supplementary Riboflavin in the SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis (FALS). Lasers Surg Med. 2009;41(1):52-59.
Zhang L, Xing D, Zhu D, Chen Q. Low-power laser irradiation inhibiting Abeta25-35-induced PC12 cell apoptosis via PKC activation. Cell Physiol Biochem. 2008;22(1-4):215-222.
Michalikova S, Ennaceur A, van Rensburg R, Chazot PL. Emotional responses and memory performance of middle-aged CD1 mice in a 3D maze: effects of low infrared light. Neurobiol Learn Mem. 2008;89(4):480-488.
Trimmer PA, Schwartz KM, Borland MK, De Taboada L, Streeter J, Oron U. Reduced axonal transport in Parkinson's disease cybrid neurites is restored by light therapy. Mol Neurodegener. 2009;4:26.
Shaw VE, Spana S, Ashkan K, et al. Neuroprotection of midbrain dopaminergic cells in MPTP-treated mice after near-infrared light treatment. J Comp Neurol. 2010;518(1):25-40.
Valla J, Berndt JD, Gonzalez-Lima F. Energy hypometabolism in posterior cingulate cortex of Alzheimer's patients: superficial laminar cytochrome oxidase associated with disease duration. J Neurosci. 2001;21(13):4923-4930.
Valla J, Yaari R, Wolf AB, et al. Reduced posterior cingulate mitochondrial activity in expired young adult carriers of the APOE ?4 allele, the major late-onset Alzheimer's susceptibility gene. J Alzheimers Dis. 2010;22(1):307-313.
Schiffer F, Johnston AL, Ravichandran C, et al. Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety. Behav Brain Funct. 2009;5:46.
Askalsky P, Iosifescu DV. Transcranial Photobiomodulation For The Management Of Depression: Current Perspectives. Neuropsychiatr Dis Treat. 2019;15:3255-3272. Published 2019 Nov 22.
Anders JJ, Geuna S, Rochkind S. Phototherapy promotes regeneration and functional recovery of injured peripheral nerve. Neurol Res. 2004;26(2):233-239.
Gigo-Benato D, Geuna S, Rochkind S. Phototherapy for enhancing peripheral nerve repair: a review of the literature. Muscle Nerve. 2005;31(6):694-701.
Leavitt M, Charles G, Heyman E, Michaels D. HairMax LaserComb laser phototherapy device in the treatment of male androgenetic alopecia: A randomized, double-blind, sham device-controlled, multicentre trial. Clin Drug Investig. 2009;29(5):283-292.
Muste JC, Russell MW, Singh RP. Photobiomodulation Therapy for Age-Related Macular Degeneration and Diabetic Retinopathy: A Review. Clin Ophthalmol. 2021;15:3709-3720.
Jarrett SG, Boulton ME. Consequences of oxidative stress in age-related macular degeneration. Mol Aspects Med. 2012;33(4):399-417.
Kokkinopoulos I, Colman A, Hogg C, Heckenlively J, Jeffery G. Age-related retinal inflammation is reduced by 670 nm light via increased mitochondrial membrane potential. Neurobiol Aging. 2013;34(2):602-609.
Eells JT. Mitochondrial Dysfunction in the Aging Retina. Biology (Basel). 2019;8(2):31.
Ennis S, Gibson J, Cree AJ, Collins A, Lotery AJ. Support for the involvement of complement factor I in age-related macular degeneration. Eur J Hum Genet. 2010;18(1):15-16.
Begum R, Powner MB, Hudson N, Hogg C, Jeffery G. Treatment with 670 nm light up regulates cytochrome C oxidase expression and reduces inflammation in an age-related macular degeneration model. PLoS One. 2013;8(2):e57828.
Ivandic BT, Ivandic T. Low-level laser therapy improves vision in patients with age-related macular degeneration. Photomed Laser Surg. 2008;26(3):241-245.
Merry G, Dotson R, Devenyi R, Markowitz SRS. Photobiomodulation as a new treatment for dry age related macular degeneration RESULTS from the Toronto and Oak Ridge Photobimodulation study in AMD (TORPA). Invest Ophthalmol Vis Sci. 2012;53:2049.
Merry GF, Munk MR, Dotson RS, Walker MG, Devenyi RG. Photobiomodulation reduces drusen volume and improves visual acuity and contrast sensitivity in dry age-related macular degeneration. Acta Ophthalmol. 2017;95(4):e270-e277.
Markowitz SN, Devenyi RG, Munk MR, et al. A double-masked, randomized, sham-controlled, single-center study with photobiomodulation for the treatment of dry age-related macular degeneration. Retina. 2019;40:1471.
Sergienko AM, Dzuba NO, Pekarik OS. Changes of the optic density of the macular pigment after two courses of low-energy light therapy in patients with dry form of age-related macular degeneration. Oftalmol Zh.2014;5:40-44
Muste JC, Kalur A, Iyer A, Valentim CCS, Singh RP. Photobiomodulation therapy in age-related macular degeneration. Curr Opin Ophthalmol. 2021;32(3):225-232.
Cheng Y, Du Y, Liu H, Tang J, Veenstra A, Kern TS. Photobiomodulation Inhibits Long-term Structural and Functional Lesions of Diabetic Retinopathy. Diabetes. 2018;67(2):291-298.
Saliba A, Du Y, Liu H, et al. Photobiomodulation Mitigates Diabetes-Induced Retinopathy by Direct and Indirect Mechanisms: Evidence from Intervention Studies in Pigmented Mice. PLoS One. 2015;10(10):e0139003.
Tang J, Herda AA, Kern TS. Photobiomodulation in the treatment of patients with non-center-involving diabetic macular oedema [published correction appears in Br J Ophthalmol. 2014 Oct;98(10):1463. Dosage error in article text]. Br J Ophthalmol. 2014;98(8):1013-1015.
Shen W, Teo KYC, Wood JPM, et al. Preclinical and clinical studies of photobiomodulation therapy for macular oedema. Diabetologia. 2020;63(9):1900-1915.
Kim JE, Glassman AR, Josic K, et al. A Randomized Trial of Photobiomodulation Therapy for Center-Involved Diabetic Macular Edema with Good Visual Acuity (Protocol AE). Ophthalmol Retina. 2022;6(4):298-307.
Ivandic BT, Ivandic T. Low-level laser therapy improves vision in a patient with retinitis pigmentosa. Photomed Laser Surg. 2014;32(3):181-184.
Scalinci SZ, Valsecchi N, Pacella E, Trovato Battagliola E. Effects of Photo-Biomodulation in Stargardt Disease. Clin Ophthalmol. 2022;16:85-91.
Ng WSV, Trigano M, Freeman T, et al. New avenues for therapy in mitochondrial optic neuropathies. Therapeutic Advances in Rare Disease. January 2021.
Albarracin R, Eells J, Valter K. Photobiomodulation protects the retina from light-induced photoreceptor degeneration. Invest Ophthalmol Vis Sci. 2011;52(6):3582-3592.
Eells JT, Henry MM, Summerfelt P, et al. Therapeutic photobiomodulation for methanol-induced retinal toxicity. Proc Natl Acad Sci U S A. 2003;100(6):3439-3444.
Ivandic BT, Ivandic T. Low-level laser therapy improves visual acuity in adolescent and adult patients with amblyopia. Photomed Laser Surg. 2012;30(3):167-171.
Guzun OV, Boichuk IM, Chechin PP, Khramenko NI, Konovalova NV. Laser Stimulation of Retina and Optic Nerve in Children with Anisometropic Amblyopia. 2019 IEEE 8th International Conference on Advanced Optoelectronics and Lasers (CAOL). 2019,;1-5.
Schwartz M, Doron A, Erlich M, et al. Effects of low-energy He-Ne laser irradiation on posttraumatic degeneration of adult rabbit optic nerve. Lasers Surg Med. 1987;7(1):51-55.
Assia E, Rosner M, Belkin M, Solomon A, Schwartz M. Temporal parameters of low energy laser irradiation for optimal delay of post-traumatic degeneration of rat optic nerve. Brain Res. 1989;476(2):205-212.
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