Non-damaging laser treatment with electroretinography-based thermal dosimetry activates hormetic heat response in pig retinal pigment epithelium

Enhancing protein homeostasis and antioxidant defense mechanisms in the retinal pigment epithelium (RPE) holds significant promise as a treatment option for various retinal diseases, including age-related macular degeneration. However, patient responses to laser-induced RPE hyperthermia varies substantially. To address this, we introduce a focal electroretinography (fERG)-based method for retinal temperature monitoring during laser exposure. Applying the method to anaesthetized male pigs in vivo, we study the biological effects of controlled retinal hyperthermia. Our findings reveal that temperature elevation to 44 °C with 60-second laser exposure triggers heat shock protein production and autophagy activation in RPE/choroid while avoiding oxidative stress, apoptosis, and structural damage. Importantly, our results demonstrate that visible lesions occur at temperatures above 48 °C, and that the temperature determination precision was 0.6 °C. These outcomes highlight that fERG-controlled retinal laser treatment enables reliable and safe activation of cytoprotective mechanisms in the RPE, providing a promising new therapeutic approach.