Retinal Toxicity Service

Newcells provides retinal toxicity studies using our highly reproducible iPSC-derived human models (retinal organoids and RPE) to provide you with predictive data

With a streamlined manufacturing process releasing regular supply of high quality tissue, projects timelines are usually short and a study is usually carried out within two months. The predictive data generated by our scientific experts will therefore allow you to rapidly assess the ocular toxicity profile of your drugs to guide key decision-making steps during drug development or regulatory submissions.

An example of retinal drug toxicity screening includes a set of assays to assess cell viability, photoreceptor functionality and degeneration as well as analysis of key marker expression and localisation to test novel drug compounds and viral vectors such as AAV.

What is retinal toxicity and how can it be evaluated in vitro? Some drugs administered systematically may affect the function of the retina. Similarly, new treatments for eye diseases require careful safety evaluation. Retinal toxicity studies can be performed in animal models, or human ex-vivo models. However, these are limiting due to the number of experimental data points that can be generated and limited predictivity in humans.

Newcells scientists have developed robust toxicity assays run on their highly reproducible and readily available iPSC-derived human organoids or RPE models that recapitulate the in vivo environment.

Retinal organoids are obtained through a carefully controlled differentiation process recapitulating the timeline of embryonic retinogenesis. At day 150, the organoids comprise all key cell types and are functional, allowing the detailed evaluation of the cytotoxic effect of new compounds by simply adding them to the plate. The cell structure integrity and the gene expression profiles of key markers for the main cell types, such as photoreceptors, are also assessed following addition of the drug. We subsequently perform qualitative imaging and microscopy analysis to provide a comprehensive drug toxicity profile.

Uniquely, the RPE cells are derived from healthy donor iPSCs from the same genetic background as retinal organoids, allowing parallel and isogenic assessment of both RPE and neurosensory retina. The plates format of the RPE model allows for flexibility in dosing and analytical readouts in toxicity studies, including morphology assessment of the cells and functional assessment such as RPE-analysis of phagocytosis of photoreceptor outer segments and trans-epithelial resistance (TEER).

As our assays are preformed with models derived from human iPSCs, they are directly relevant to human clinical trials, and provide key toxicology predictive data for translational studies. The two main advantages of outsourcing your in vitro retinal toxicity study are the speed (as most simple studies can be carried out within one to two months) and the data predictivity for human clinical trials.

Retinal drug toxicity study in retinal organoids: The response of retinal organoids to exposure of known toxins such as thioridazine and doxorubicin. The intrinsic fluorescence of doxorubicin facilitates visualisation of the drug penetrating the retinal organoid (A). Exposure of the iPSC-derived retinal organoids to doxorubicin reduces cell viability in a dose-dependent manner (B).

During early drug development, drug screening is an essential step for the identification of lead compounds. This is usually performed as medium to high throughput. Newcells Biotech retinal organoids are suitable for in vitro drug screening since they are generated every 4-6 weeks (on-demand supply) in a 96-well plate format. They have been used to distinguish compounds which are toxic and non-toxic to the retina.