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      A Novel Method for Mouse Retinal Temperature Determination Based on ERG Photoresponses

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          Abstract

          This study introduces a novel retinal temperature determination method based on the temperature dependent properties of photoresponses recorded by electroretinography (ERG). The kinetics and amplitudes of ERG photoresponses depend on retinal temperature. Additionally, raising retinal temperature increases the probability of long-wavelength photon absorption, which manifests as temperature dependence of photoreceptor sensitivity. In this study we extract a number of features that represent these properties from the a- and b-waves of mouse ex vivo ERG flash responses and construct three multivariable regression models between temperature and the selected features. The performance of these models was evaluated against a separate test dataset and for two of the models, an RMS temperature determination error of less than 0.50 °C could be reached. Our results demonstrate that the method can be successfully used for reliable retinal temperature determination ex vivo. The method, reflecting the temperature of distal retina, can be applied also in the estimation of retinal pigment epithelium temperature.

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          Most cited references34

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          B-wave of the electroretinogram. A reflection of ON bipolar cell activity

          Light-evoked intraretinal field potentials (electroretinogram, ERG) have been measured simultaneously with extracellular potassium fluxes in the amphibian retina. The application of highly selective pharmacologic agents permitted us to functionally isolate various classes of retinal neurons. It was found that: (a) application of APB (2-amino-4-phosphonobutyrate), which has previously been shown to selectively abolish the light responsiveness of ON bipolar cells, causes a concomitant loss of the ERG b-wave and ON potassium flux. (b) Conversely, PDA (cis 2,3-piperidine-dicarboxylic acid) or KYN (kynurenic acid), which have been reported to suppress the light responses of OFF bipolar, horizontal, and third-order retinal neurons, causes a loss of the ERG d-wave as well as OFF potassium fluxes. The b- wave and ON potassium fluxes, however, remain undiminished. (c) NMA (N- methyl-DL-aspartate) or GLY (glycine), which have been reported to suppress the responses of third-order neurons, do not diminish the b- or d-waves, nor the potassium fluxes at ON or OFF. This leads to the conclusion that the b-wave of the ERG is a result of the light-evoked depolarization of the ON bipolar neurons. This experimental approach has resulted in two further conclusions: (a) that the d-wave is an expression of OFF bipolar and/or horizontal cell depolarization at the termination of illumination and (b) that light-induced increases in extracellular potassium concentration in both the inner (proximal) and outer (distal) retina are the result of ON bipolar cell depolarization.
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            Activation of visual pigments by light and heat.

            Vision begins with photoisomerization of visual pigments. Thermal energy can complement photon energy to drive photoisomerization, but it also triggers spontaneous pigment activation as noise that interferes with light detection. For half a century, the mechanism underlying this dark noise has remained controversial. We report here a quantitative relation between a pigment's photoactivation energy and its peak-absorption wavelength, λ(max). Using this relation and assuming that pigment activations by light and heat go through the same ground-state isomerization energy barrier, we can predict the relative noise of diverse pigments with multi-vibrational-mode thermal statistics. The agreement between predictions and our measurements strongly suggests that pigment noise arises from canonical isomerization. The predicted high noise for pigments with λ(max) in the infrared presumably explains why they apparently do not exist in nature.
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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

                Contributors
                +358 50 367 3768 , ari.koskelainen@aalto.fi
                Journal
                Ann Biomed Eng
                Ann Biomed Eng
                Annals of Biomedical Engineering
                Springer US (New York )
                0090-6964
                1573-9686
                15 June 2017
                15 June 2017
                2017
                : 45
                : 10
                : 2360-2372
                Affiliations
                ISNI 0000000108389418, GRID grid.5373.2, Department of Neuroscience and Biomedical Engineering, , Aalto University School of Science, ; P.O. Box 12200, 00076 Aalto, Finland
                Author notes

                Associate Editor Tingrui Pan oversaw the review of this article.

                Article
                1872
                10.1007/s10439-017-1872-y
                5622180
                28620767
                333ef7bc-82a1-4b48-ae87-3f3d238f65c2
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 18 February 2017
                : 9 June 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100002341, Suomen Akatemia;
                Award ID: 269747
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100003125, Suomen Kulttuurirahasto;
                Categories
                Article
                Custom metadata
                © Biomedical Engineering Society 2017

                Biomedical engineering
                electroretinography,retina,retinal pigment epithelium,kinetics,temperature-dependence

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