Retinal Temperature Determination Based on Photopic Porcine Electroretinogram

Kaikkonen, Ossi; Turunen, Teemu; Meller, Anna; Åhlgren, Johanna; Koskelainen, Ari

doi:10.1109/tbme.2021.3111533

Cited by 4 publications

(8 citation statements)

References 43 publications

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“…However, the therapeutic temperature window for subthreshold heat shock is narrow and requires accurate temperature control of the RPE during heating [ 26 ]. This may be achieved by the retinal temperature determination method developed in the research group of Koskelainen [ 65 , 66 , 67 ], thereby counteracting the progress of age-related macular degeneration.…”

Section: Discussionmentioning

confidence: 99%

Hormetic Heat Shock Enhances Autophagy through HSF1 in Retinal Pigment Epithelium Cells

Amirkavei

Plastino

Kvanta

et al. 2022

Cells

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To maintain homeostasis, cells have evolved stress-response pathways to cope with exogenous and endogenous stress factors. Diverse stresses at high doses may be detrimental, albeit low doses of stress, known as hormesis, can be beneficial. Upon exposure to stress, such as temperature rise, the conventional heat shock response (HSR) regulated by the heat shock transcription factor 1 (HSF1) facilitates refolding of misfolded proteins with the help of heat shock proteins (HSPs). However, the role and molecular mechanisms underlying the beneficial effects of HSR with other clearance processes, such as autophagy, remain poorly understood. In this study, human ARPE-19 cells, an in vitro model of retinal pigment epithelium, were treated with hormetic heat shock (HHS) and the autophagy expression profile was examined using quantitative PCR (qPCR), immunoblotting, immunoprecipitation, and immunofluorescence. We demonstrate that HHS enhances the expression of fundamental autophagy-associated genes in ARPE-19 cells through the activation of HSF1. HHS transiently increases the level of SQSTM1 and LC3B-II and activates autophagy. These findings reveal a role for autophagic HSF1-regulated functions and demonstrate the contribution of autophagy to hormesis in the HSR by improving proteostasis.

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Section: Discussionmentioning

confidence: 99%

Hormetic Heat Shock Enhances Autophagy through HSF1 in Retinal Pigment Epithelium Cells

Amirkavei

Plastino

Kvanta

et al. 2022

Cells

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“…The temperature determination algorithm, shown in Eq. 2 and described with further detail in (Kaikkonen et al ., 2021), takes two ERG responses f 1 ( t ) and f 2 ( t ) as inputs, with t = 0 set to the moment of the flash stimulus, and determines the difference in retinal temperature Δ T between two ERG responses. A value of 3.7 %/ °C was used for the temperature dependence of kinetics acceleration, as determined for pig cones with similar stimulus-background illumination contrast in (Kaikkonen et al ., 2021, their Fig.…”

Section: Methodsmentioning

confidence: 99%

“…The anesthesia was induced as described in (Kaikkonen et al ., 2021). Before each anesthesia, the pigs fasted at least 17 hours.…”

Section: Methodsmentioning

confidence: 99%

“…Despite the narrow therapeutic window and the variation in individual physiological properties, thermal dosimetry for retinal laser treatments is currently unavailable. Electroretinography (ERG), a registration of a field potential generated by retinal neurons, is a promising method for thermal dosimetry of SLTs since ERG signaling kinetics are strongly temperaturedependent Koskelainen, 2017, 2019;Kaikkonen et al, 2021). In ERG registration, the retina is stimulated with light and the resulting signal can be recorded non-invasively using corneal and skin electrodes.…”

Section: Introductionmentioning

confidence: 99%

“…Electroretinography (ERG), a registration of a field potential generated by retinal neurons, is a promising method for thermal dosimetry of SLTs since ERG signaling kinetics are strongly temperature-dependent (Pitkänen, Kaikkonen and Koskelainen, 2017, 2019; Kaikkonen et al ., 2021). In ERG registration, the retina is stimulated with light and the resulting signal can be recorded non-invasively using corneal and skin electrodes.…”

Section: Introductionmentioning

confidence: 99%

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Novel subthreshold retinal laser treatment with ERG-based thermal dosimetry activates hormetic heat response in pig RPEin vivo

Amirkavei

Kaikkonen

Turunen

et al. 2022

Preprint

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Boosting natural mechanisms to retain cellular homeostasis and combat oxidative stress by inducing a hormetic heat shock to retinal pigment epithelium with non-damaging transpupillary laser heating, i.e., with subthreshold laser treatment (SLT), has been suggested as a promising therapeutic target for many retinal diseases, including age-related macular degeneration. However, the therapeutic temperature window for the treatments is narrow and thermal dosimetry is unavailable. Here we introduce an SLT modality where the retinal temperature is monitored with electroretinography (ERG)-based thermal dosimetry and demonstrate its feasibility with anesthetized pigs. In 60-second treatments with 810 nm laser, the ED50 peak temperature for visible lesion generation was 48 °C and the relative temperature determination error was below 10% from the temperature increase. Heat shock protein expression increased, and autophagy was activated at 44.2 °C and no signs of oxidative stress or apoptosis emerged at 44.2 °C or 46.5 °C. The demonstrated method permits a controlled activation of intracellular chaperones and waste clearance in RPE cell with a clear temperature margin for adverse events. In the clinical setting, ERG-based dosimetry would allow safe and personalized SLTs for retinal diseases currently lacking effective treatments.

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Regenerative Retinal Laser and Light Therapies (RELITE): Proposal of a New Nomenclature, Categorization, and Trial Reporting Standard

von der Burchard,

Miura,

Stanzel

et al. 2024

Lasers Surg Med

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ObjectivesNumerous laser and light therapies have been developed to induce regenerative processes in the choroid/retinal pigment epithelium (RPE)/photoreceptor complex, leaving the neuroretina undamaged. These therapies are applied to the macula for the treatment of various diseases, most prominently diabetic maculopathy, retinal vein occlusion, central serous chorioretinopathy, and age‐related macular degeneration. However, the abundance of technologies, treatment patterns, and dosimetry protocols has made understanding these therapies and comparing different approaches increasingly complex and challenging. To address this, we propose a new nomenclature system with a clear categorization that will allow for better understanding and comparability between different laser and light modalities. We propose this nomenclature system as an open standard that may be adapted in future toward new technical developments or medical advancements.MethodsA systematic literature review of reported macular laser and light therapies was conducted. A categorization into a standardized system was proposed and discussed among experts and professionals in the field. This paper does not aim to assess, compare, or evaluate the efficacy of different laser or dosimetry techniques or treatment patterns.ResultsThe literature search yielded 194 papers describing laser techniques, 50 studies describing dosimetry, 272 studies with relevant clinical trials, and 82 reviews. Following the common therapeutic aim, we propose “regenerative retinal laser and light therapies (RELITE)” as the general header. We subdivided RELITE into four main categories that refer to the intended physical and biochemical effects of temperature increase (photothermal therapy, PTT), RPE regeneration (photomicrodisruption therapy, PMT), photochemical processes (photochemical therapy, PCT), and photobiomodulation (photobiomodulation therapy, PBT).Further, we categorized the different dosimetry approaches and treatment regimens. We propose the following nomenclature system that integrates the most important parameters to enable understanding and comparability:Pattern—Dosimetry—Exposure Time/Frequency, Duty Cycle/Irradiation Diameter/Wavelength—Subcategory—Category.ConclusionRegenerative retinal laser and light therapies are widely used for different diseases and may become valuable in the future. A precise nomenclature system and strict reporting standards are needed to allow for a better understanding, reproduceable and comparable clinical trials, and overall acceptance. We defined categories for a systematic therapeutic goal‐based nomenclature to facilitate future research in this field.

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Retinal Temperature Determination Based on Photopic Porcine Electroretinogram

Cited by 4 publications

References 43 publications

Hormetic Heat Shock Enhances Autophagy through HSF1 in Retinal Pigment Epithelium Cells

Hormetic Heat Shock Enhances Autophagy through HSF1 in Retinal Pigment Epithelium Cells

Novel subthreshold retinal laser treatment with ERG-based thermal dosimetry activates hormetic heat response in pig RPEin vivo

Regenerative Retinal Laser and Light Therapies (RELITE): Proposal of a New Nomenclature, Categorization, and Trial Reporting Standard

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