Periodic Reporting for period 2 - ENTRAIN VISION (European Network for integrated TRAINing on Innovative Therapies for VISion RestoratiON)
Reporting period: 2022-04-01 to 2024-09-30
Blindness is the most feared handicap. It is leading to a complete exclusion from society by reducing patient autonomy and mobility. There are still an estimated 285 million vision impaired and 39 million blind people worldwide. Due to population growth and ageing, the number of blind people or visually-impaired people could triple by 2050. Treatments are urgently needed to prevent this aging-related increase in the population of visually impaired patients. This growth is also highly related to our change in lifestyle leading to the epidemics of diabetic retinopathy and myopia. The present ENTRAIN-Vision project aims at preparing Early Stage Researchers who will have a comprehensive view of new therapeutic approaches to vision restoration so that they can take part in future Research and Development, or in their future deployment throughout Europe. During the project, the different ESR have worked on the development of novel innovative technologies for visual restoration at both the retinal and cortical levels.
Innovation is required to generate new technologies allowing greater visual acuity with either electronic prostheses or optogenetic therapy. ESRs will first assess these technologies on blind rodents by functional measurements including behavioral tests to then evaluate them in larger animals preparing thereby the translation to human patients. In this clinical translation, they will also perform computational modeling to properly design the stimulation protocols. Finally, they will define clinical endpoints for the validation of such innovative technologies. This Project will therefore train broadly skilled ESRs in innovative strategies and technologies for visual restoration.
During the first two years, the project results include advances with regards to
- Preclinical validation of prosthesis: characterization and testing of materials to develop a subretinal prosthesis with the investigation of the beneficial and adverse effects of electrical stimulation on the retinal tissue
- Preclinical validation of visual restoration by chemical and biological photoswitches: Evaluation of novel therapeutic strategies by using photoswitchable molecules targeted to the plasma membrane of retinal neurons and the analysis of the retinal responses to natural images, electrical or optogenetic stimulations. resulting in the identification and description of a subclass of retinal ganglion cells that are believed to encode for the contrast present in the visual images, electrophysiological recordings of single retinas in response to electrical or optogenetic stimuli, From natural vision to model for artificial vision: Modeling the electrical or optogenetic stimulation parameters to achieve long-term performance of the devices and perform usefull daily tasks
- Visual perception during retinal diseases in animal models and patients: Segregation of retinal cells according to their electric/dielectric properties for classification in different pathological conditions, behavioral assessment and modeling of the animal performance according to the disease states, interpretation of anatomical and functional 7T fMRI scan for a future cortical visual prosthesis recipient, Production of protocoles to assess the improvement of the quality of life in terms of daily activities.
During the first two years, the project results include advances with regards to
- Preclinical validation of prosthesis: characterization and testing of materials to develop a subretinal prosthesis with the investigation of the beneficial and adverse effects of electrical stimulation on the retinal tissue
- Preclinical validation of visual restoration by chemical and biological photoswitches: Evaluation of novel therapeutic strategies by using photoswitchable molecules targeted to the plasma membrane of retinal neurons and the analysis of the retinal responses to natural images, electrical or optogenetic stimulations. resulting in the identification and description of a subclass of retinal ganglion cells that are believed to encode for the contrast present in the visual images, electrophysiological recordings of single retinas in response to electrical or optogenetic stimuli, From natural vision to model for artificial vision: Modeling the electrical or optogenetic stimulation parameters to achieve long-term performance of the devices and perform usefull daily tasks
- Visual perception during retinal diseases in animal models and patients: Segregation of retinal cells according to their electric/dielectric properties for classification in different pathological conditions, behavioral assessment and modeling of the animal performance according to the disease states, interpretation of anatomical and functional 7T fMRI scan for a future cortical visual prosthesis recipient, Production of protocoles to assess the improvement of the quality of life in terms of daily activities.
The ENTRAIN Vision project has enlarged our knowledge on the the visual information processing while developing novel strategies to prevent the visual loss in ocular diseases or restoring vision in blind patients with the implementation of novel protocols to demonstrate the efficacy of these innovations in preclinical and clinical conditions. For instance, the ESRs have developed innovations in molecules such as photoswitch or in materials included in visual prostheses or nanoparticles. Innovative solutions were also on the design of visual prostheses such as the increase in visual angle or on the design of optical devices for the optogenetic therapy to accurately stimulate optically visual neurons based on their morphologies. The clinical studies of cortical prostheses have demonstrated the efficacy of stimulating the visual cortex in its depth to restore some visual function in blind patients. Furthermore, the analysis of the long-term recording of the blind patients allowed the development of novel strategies to enhance the efficacy of visual prostheses by establishing closed loop recording-stimulation procedures. Finally, a novel test for mobility and orientation was implemented in real conditions and then in virtual reality goggles providing thereby a unique approach to evaluate the efficacy of therapeutic and rehabilitation strategies.
The results of the ENTRAIN project will have a major socio-economic impact with wide societal implications because ocular diseases are greatly increasing due to the aging of the population and the myopic epidemic. Indeed, the number of visually impaired patients will triple before 2050 while blind patients are expected to double in the period. Therefore, the development of innovations by the ENTRAIN Vision project for preventing the evolution of these ocular diseases or for restoring vision will greatly impact these health challenges for our societies. Especially, the highly talented ESR scientists will have the knowledge and faculty to play a key role in implementing these innovations for the patients in the academic and industrial entities.
The results of the ENTRAIN project will have a major socio-economic impact with wide societal implications because ocular diseases are greatly increasing due to the aging of the population and the myopic epidemic. Indeed, the number of visually impaired patients will triple before 2050 while blind patients are expected to double in the period. Therefore, the development of innovations by the ENTRAIN Vision project for preventing the evolution of these ocular diseases or for restoring vision will greatly impact these health challenges for our societies. Especially, the highly talented ESR scientists will have the knowledge and faculty to play a key role in implementing these innovations for the patients in the academic and industrial entities.