Biology subjects

Koskelainen, A.

Publications and source records attributed to Koskelainen, A..

2 recordsLinked to original sources

bioRxiv2024

Restoring and sustaining human postmortem retinal light responses with scalable methods for testing degenerative disease therapies

Neuro- and retinal degenerative diseases, including Alzheimers, age-related macular degeneration, stroke, and central retinal artery occlusion, rob millions of their independence. Studying these diseases in human retinas has been hindered by the immediate loss of neuronal activity postmortem. While recent studies restored limited activity in postmortem CNS tissues, synchronized neuronal transmission >30 minutes postmortem remained elusive. Our study overcomes this barrier by reviving and sustaining light signal transmission in human retinas recovered up to four hours and stored 48 hours postmortem. We also establish infrared-based ex vivo imaging for precise sampling, a closed perfusion system for drug testing, and an ex vivo ischemia-reperfusion model in mouse and human retina. This platform enables testing of neuroprotective and neurotoxic effects of drugs targeting oxidative stress and glutamate excitotoxicity. Our advances question the irreversibility of ischemic injury, support preclinical vision restoration studies, offer new insights into treating ischemic CNS injuries, and pave the way for transplantation of human donor eyes. TeaserReviving light signaling in postmortem human retinas challenges the irreversibility of ischemic injury and advances research to restore vision.

neuroscience↗

bioRxiv2022

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

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{degrees}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 {degrees}C and no signs of oxidative stress or apoptosis emerged at 44.2 {degrees}C or 46.5 {degrees}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.

bioengineering↗