Activating an optogenetically engineered retina with a wearable headset in patients with retinitis pigmentosa

• Published in: Acta ophthalmologica (Oxford, England) Vol. 97; no. S263
• Main Authors: Chavas, Joël, Boussahoul, Nacer, Duport, Damien, Galle, Charlie, Galluppi, Francesco, Blouin, Laure, Burguière, Pierre, Hardin, Thomas, Shabestary, Proshato, Gray, David
• Format: Journal Article
• Language: English
• Published: Malden Wiley Subscription Services, Inc 01.12.2019
• Subjects: Activation; Animal models; Exposure; Genetics; Information processing; Irradiance; Light; Light intensity; Medical devices; Medical electronics; Medical equipment; Optics; Patients; Photons; Primates; Retina; Retinal ganglion cells; Retinitis; Retinitis pigmentosa; Software engineering; Statistical analysis
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/j.1755-3768.2019.5371

Purpose Optogenetics allows the expression of channelrhodopsins like ChrimsonR (ChR) in the retina of blind patients in order to confer light sensitivity to retinal ganglion cells (RGCs). However, ChR has a low sensitivity to light and is unlikely to be activated by ambient light. To activate ChR and to obtain a functional response from the RGCs, we developed and tested a wearable headset that delivers light stimulation to the human retina at an appropriate irradiance and wavelength. Methods We designed and constructed a wearable headset using electronics, optics, mechanics and software engineering. The proper range of light intensity required for the activation of ChR fused with tdTomato (ChRtdT) was tested on explanted retinas of non‐human primates (NHPs) transfected with AAV2.7m8‐ChRtdT. The ocular safety of exposure to 595 nm LED light following intravitreal injection of AAV2.7m8‐ChRdtT was assessed in rd1 mice, an established animal model for retinitis pigmentosa. Results Activation of ChRtdT in explanted retinas of NHPs transfected with AAV2.7m8‐ChRtdT showed that a minimum of 1015 photons/cm2/s (0.33 mW/cm2) of amber light was required to get a statistically significant electrophysiological response. In rd1 mice transfected with AAV2.7m8‐ChRtdT, fourteen days after exposure to 595‐nm LED light for 2 hours, no light‐related findings were identified in the retina at the highest intensity tested (nominal 1.7 × 1017 photons/cm2/s). As a result, our wearable headset provides a retinal irradiance up to 4 × 1016 photons/cm2/s for a period leading to a dose matching the one received by the retina of rd1 mouse exposed for 2 hours, a level shown to be safe for the retina. Conclusion Our medical device GS030‐MD was designed to send a light irradiance to the human retina both sufficient to activate ChRtdT and safe for the eye. GS030‐MD is currently being tested in combination with AAV2.7m8‐ChRtdT in the first‐in‐man PIONEER Phase I/II clinical trial.