Periodic Reporting for period 1 - OPTIMEYEZ (Optical imaging platform for high-throughput longitudinal studies of the eye in disease models)
Berichtszeitraum: 2023-10-01 bis 2025-03-31
Vision loss is often linked to retinal disorders, which can be primary or secondary, such as those involved in metabolic or neurological conditions. As the retina is an easily accessible extension of the brain, it has become a prime target for non-invasive diagnostics of neurological diseases like Alzheimer's. Preclinical testing in rodents is crucial for developing new therapeutic compounds. The standard for such research relies on histological confirmation, which necessitates sacrificing the animals. In contrast, optical imaging methods allow for the quick identification of pathological tissue structures using intrinsic contrast. In the ERC Starting Grant OPTIMALZ, we developed a novel multi-contrast optical imaging platform for longitudinal retinal studies. Our prototype, based on high-speed optical coherence tomography (OCT) technology, provides 3D images from light backscattered from the retina, polarization contrast for identifying pigmented lesions, and OCT angiography for visualizing microvasculature without contrast agents. Unlike histology, our platform enables repeated, non-invasive imaging of live rodent eyes, significantly reducing the number of animals needed for studies. We have successfully demonstrated our technology's potential in rodent models of primary retinal degeneration and Alzheimer’s disease. The PoC project OPTIMEYEZ aimed to expand our imaging portfolio to include additional disease models, improve technological aspects, and make our platform accessible to key pharmaceutical industry players.
OPTIMEYEZ aimed to establish our imaging platform developed in ERC Starting Grant OPTIMALZ for high-throughput longitudinal studies in eye-brain research. Our steps towards the exploration of the innovation potential were focused on four aspects. (1) Drastic improvement of the usability of the platform by implementing a high-speed data analysis pipeline with an easy-to-use interface: We improved our technology for both acquisition and image analysis. By upgrading the acquisition hardware and implementing more flexible acquisition options as well as by taking our data analysis pipeline to the next level, our prototype was optimized to provide fast, smooth and reliable imaging as well as more streamlined yet flexible evaluation of the acquired OCT data. In parallel, novel OCT approaches and new data analysis methods were devised and explored. (2) Demonstration of the feasibility to identify subtle phenotypic differences in retinal pathologies of relevant mouse models harboring three different genetic mutations relevant for human Alzheimer’s disease (AD): Longitudinal studies were performed in several models of amyloidosis and presenilin-related genetic mutations. We used OCT in parallel with state-of-the-art behavioral testing and investigated the correlation of structural alterations in the retina with phenotypic changes of spatial memory. Distinct differences dependent on genotype and sex were discovered in a longitudinal investigation of spatial memory and retinal parameters in a 5xFAD model of AD. An in-depth evaluation and comparison of OCT parameters observed in different AD models is ongoing. (3) Teaming up with a contract research organization (CRO) to approach pharmacologically targeted research and make our technology accessible to end-users: We joined forces with a CRO and explored AD models, also leading to the findings described for aim (2) above. Short-time joint funding was obtained. (4) Implementation of a strategy for securing intellectual property and further commercialization: Our initial route for IP was defeated by a competing patent, however an alternative technological novelty was identified and may be exploited beyond the end of the PoC project. In addition, we took several strategic steps towards approaching potential end-users, including the installation of a booth at the exhibition of the ARVO Annual Meeting 2024 in Seattle. There, the OPTIMEYEZ team was approached by and interacted with interested researchers as well as companies in the field of imaging and retinal diseases, starting bonds for further exploitation of our technology and scientific collaboration.
OPTIMEYEZ was designed to further advance the technology developed in OPTIMALZ, aimed to expand the application range through imaging studies in additional disease models, improve the prototype’s technological implementation, and make our platform accessible to key players in pharmaceutical industry. In addition to several preclinical studies in disease models with different genetic modifications related to AD as outlined above, we also investigated the impact of different experimental protocols on the measured OCT parameters. Thereby, we identified important dependencies on the chosen investigational approach, hence revealing the current lack of standardization. We also explored novel technological approaches enabling access to additional tissue characteristics that can only be obtained by in-vivo imaging. However, while no intellectual property was secured within the framework of OPTIMEYEZ, we did identify alternative technological advancements that have the potential for innovation and will be pursued further by our team towards a potential patent application. Finally, the fruitful attempts to team up with potential end-users have enabled comprehensive imaging studies and the establishment of new scientific collaborations towards next-generation biomedical eye and brain research far beyond the scope of OPTIMALZ.