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      Comparison of Subthreshold 577 and 810 nm Micropulse Laser Effects on Heat-Shock Protein Activation Kinetics: Implications for Treatment Efficacy and Safety

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          Abstract

          Purpose

          To compare the safety and efficacy of 810 versus 577 nm laser wavelengths for micropulse subthreshold (sublethal) laser treatment by mathematical analysis.

          Methods

          Two different representative laser parameter sets for micropulsed subthreshold diode laser treatment, one employing 810 nm and the other 577 nm, are compared with regard to efficacy by analysis of the kinetics of laser-induced heat-shock protein (HSP) activation; and for safety, by scaling law analysis.

          Results

          Kinetics analysis of laser-induced HSP activation shows that the primary therapeutic effect of laser is thermal incitement of a long-term wavelength-independent increase in the rate of HSP-mediated protein repair specific to sick and dysfunctional cells, rather than from short-term increases in free intracellular HSP concentrations. Scaling law analysis of the same 810 and 577 nm laser parameters, however, finds treatment safety highly wavelength-sensitive, favoring 810 over 577 nm.

          Conclusions

          Mathematical analyses of the effects retinal laser-induced HSP activation provide important insights into the mechanism of action and the importance of wavelength selection in modern retinal laser therapy. Our analyses find 810 and 577 nm to be equally effective, but 810 nm having a significantly wider therapeutic range/safety margin, and thus less likely to cause inadvertent, and thus unpredictable, laser-induced retinal damage, than 577 nm.

          Translational Relevance

          Mathematical analysis of enzyme reaction kinetics provides important insights into the mechanism of action and clinical implications of wavelength selection in modern retinal laser therapy.

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          Most cited references29

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          Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance.

          Cells from virtually all organisms respond to a variety of stresses by the rapid synthesis of a highly conserved set of polypeptides termed heat shock proteins (HSPs). The precise functions of HSPs are unknown, but there is considerable evidence that these stress proteins are essential for survival at both normal and elevated temperatures. HSPs also appear to play a critical role in the development of thermotolerance and protection from cellular damage associated with stresses such as ischemia, cytokines, and energy depletion. These observations suggest that HSPs play an important role in both normal cellular homeostasis and the stress response. This mini-review examines recent evidence and hypotheses suggesting that the HSPs may be important modifying factors in cellular responses to a variety of physiologically relevant conditions such as hyperthermia, exercise, oxidative stress, metabolic challenge, and aging.
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            Is Open Access

            Half-Dose Photodynamic Therapy versus High-Density Subthreshold Micropulse Laser Treatment in Patients with Chronic Central Serous Chorioretinopathy

            To compare the anatomic and functional efficacy and safety of half-dose photodynamic therapy (PDT) versus high-density subthreshold micropulse laser (HSML) treatment in patients with chronic central serous chorioretinopathy (cCSC).
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              Non-damaging retinal phototherapy: dynamic range of heat shock protein expression.

              Subthreshold retinal phototherapy demonstrated clinical efficacy for the treatment of diabetic macular edema without visible signs of retinal damage. To assess the range of cellular responses to sublethal hyperthermia, expression of the gene encoding a 70 kDa heat shock protein (HSP70) was evaluated after laser irradiation using a transgenic reporter mouse. One hundred millisecond, 532 nm laser exposures with 400 μm beam diameter were applied to the retina surrounding the optic nerve in 32 mice. Transcription from the HSP70 promoter was assessed relative to the control eye using a bioluminescence assay at 7 hours after laser application. The retinal pigmented epithelium (RPE) viability threshold was determined with a fluorescence assay. A computational model was developed to estimate temperature and the extent of cell damage. A significant increase in HSP70 transcription was found at exposures over 20 mW, half the threshold power for RPE cell death. Computational modeling estimated peak temperature T = 49°C at HSP70 expression threshold. At RPE viability threshold, T = 57°C. Similar temperatures and damage indices were calculated for clinical subvisible retinal treatment parameters. Beneficial effects of laser therapy have been previously shown to extend beyond those resulting from destruction of tissue. One hundred millisecond laser exposures at approximately half the threshold power of RPE damage induced transcription of HSP70, an indication of cellular response to sublethal thermal stress. A computational model of retinal hyperthermia can guide further optimization of laser parameters for nondamaging phototherapy.
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                Author and article information

                Journal
                Transl Vis Sci Technol
                Transl Vis Sci Technol
                tvst
                TVST
                Translational Vision Science & Technology
                The Association for Research in Vision and Ophthalmology
                2164-2591
                28 April 2020
                April 2020
                : 9
                : 5
                : 23
                Affiliations
                [1 ] Ojai Retinal Technologies, LLC , Ojai, CA, USA
                [2 ] Retinal Protection Sciences, LLC , Ojai, CA, USA
                [3 ] Private Practice, Ventura County Retina Vitreous Medical Group , Ventura, CA, USA
                Author notes
                Correspondence: Jeffrey K. Luttrull, 3160 Telegraph Road, Suite 230, Ventura, CA 93003, USA. e-mail info@ 123456venturacountyretina.com
                Article
                TVST-19-1947
                10.1167/tvst.9.5.23
                7401905
                32821495
                2cf2079b-fa98-43f6-8aa8-4d30ac00eac8
                Copyright 2020 The Authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 10 January 2020
                : 20 September 2019
                Page count
                Pages: 8
                Categories
                Article
                Article

                micropulse laser,subthreshold,retinal pigment epithelium,melanin,heat shock proteins,activation threshold,therapeutic range,retina,arrhenius integral

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