Retinal Toxicity Service

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 generated and limited predictivity in humans.

Newcells scientists have developed robust human iPSC-derived retinal tissue models. 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 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 then assessed. We also perform qualitative imaging and microscopy to provide a comprehensive drug toxicity profile. As our models are derived from human iPSCs, they are directly relevant to human clinical trials, and provide key data for transitional studies. The two main advantages of using in vitro retinal toxicity testing are the speed (as most simple studies can be carried out within one to two months) and the predictivity for human clinical trials.

These studies can be carried out in our retinal organoids  in vitro models for rapid evaluation of retinal toxicity of new compounds.

Modelling retinal drug toxicity: Retinal organoids have been tested for the response 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.

Newcells provides a custom service evaluating retinal toxicity using our complex iPSC-derived human retinal models (retinal organoids)

Even though the differentiation process of retinal organoids is up to 210 days, our streamlined manufacturing process releases regular supply of tissue supporting short projects timelines. The robust data generated by our scientific experts will guide you in confidence for key decision-making steps during drug development.

An example of retinal drug toxicity screening includes a set of assays to assess cell viability, photoreceptor functionality and degeneration as well as key marker expression and localisation. We can also assess the safety of new viral vectors such as AAV.