Project 451097

Subretinal injection (SI) of gene or cell therapy is a challenging surgical intervention aiming to restore and/or preserve the vision of patients suffering from retinal degenerative diseases. To perform a SI, surgeons insert a cannula under the retina, a delicate tissue layer (0.10-0.35 mm) that lines the inside of the eye and inject a small drug volume. Although this intervention is crucial for the overall therapeutic outcome, it is yet to be standardized in both humans and animal models. Mouse models are the most widely used animal models in preclinical validation of new retinal treatments. However, in mice, SI are particularly challenging due their relatively small eye. The associated drug dose administration uncertainty hinders the development of new treatments. Here, we propose to develop and validate a semi-automated optical coherence tomography (OCT) - based system, enabling controlled SI in mice. OCT is a non-invasive imaging technique that provides tomographic images of tissue. Importantly, OCT fiber probes can be used to guide surgical tools via real-time endoscopic imaging. Our goal is to develop OCT-guided SI cannulas and validate a semi-automated robotic injection system with the help of 3 end-users. The end-users will perform comparative SI in mice using a model drug and an adenovirus. Successful implementation of the project would enable unprecedented precision and repeatability in guiding modified cannulas under the mouse retina. As such, this project can timely address the unmet need for reliable subretinal drug delivery in rodents. By eliminating side effects and dose uncertainty, the novel instrument and method can catalyze the development of novel gene and cell therapies for retinal generative diseases. In the long term, potential clinical adoption of an OCT-guided SI system can facilitate the delivery of therapies aiming to restore the vision of blind people.