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Webinar: hear from our 3 panelists discussing regulatory, technology, and scientific perspectives to accelerate your compound through the clinical development pipeline with predictive retina models

A close up image of some test tubes

Retinal Toxicity

Assays

  • Cell viability assay
  • Key marker analysis
  • Quantitative immunofluorescence
  • Gene expression
  • Photoreceptor degeneration
  • Phagocytosis of photoreceptor outer segment
  • Transmission (TEM) and Scanning (SEM) electron microscopy

Models

  • Human retinal organoids
  • Derived from WT or CRISPR/Cas9 gene edited iPSCs

Timeline

  • Rapid
  • 2-6 months

Accelerated in vitro evaluation of retinal toxicity

Newcells offers a fast and reliable retinal drug toxicity in vitro testing service using complex retinal organoids models developed in house. The retinal toxicity service evaluates how new compounds affect cell viability, following photoreceptor degeneration. We also offer the comparison of several time points during differentiation. Our retinal toxicity service is fast, giving our clients insights into the ocular toxicity profile of their compounds and allowing them to evaluate possible rescue strategies.

Service outputs

  • Rapid retinal toxicity evaluation of compounds in iPSC-derived retinal organoids
  • Qualitative immunofluorescence on frozen retinal organoid sections using key markers
  • Time point comparisons
  • Assessment of the composition of retinal ganglion cells, photoreceptors, amacrine, horizontal cells and Muller glia using imaging techniques
  • Evaluation of photoreceptor degeneration
  • Analysis of loss of phagocytosis of photoreceptor outer segment

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Human retinal models

96-well format

Rapid

Newcells Retinal Models

Accelerate your lead compound selection by understanding their mode of action in functional retinal tissue

1.

Recapitulate the architecture and function of the human retina

2.

Evaluate novel drugs safety profile in vitro

3.

Accelerate drug discovery & replace animal experiments

Rapid in vitro retinal safety/efficacy assessment of new drugs: retinal toxicity made easy Close Open

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).

Retinal Toxicity 1
(A) Newcells’ human iPSC-derived retinal organoids are permeable to small molecules. The penetration of doxorubicin, a naturally fluorescent small toxic molecule (red), into the retinal organoids increases over time (4h to 24h) demonstrating the permeability of the organoids to drugs.
Retinal Toxicity 2
(B) The retinal organoids were treated with increasing dose of doxorubicin over a period of 24h and cell viability was measured using an ATP assay. A dose-dependent decrease in cell viability was observed following increasing exposure to the drug.

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.

Retinal toxicity 3
Dose-response plots of known cytotoxic and non-cytotoxic retinal agents. Retinal organoids were exposed to increasing concentrations of either cytotoxic or non-cytotoxic drugs and cell viability was measured over time. As expected, cell viability decreased upon increasing addition of Thioridazine and 4-hydrohytamoxifen, whilst non-cytotoxic drugs had no effect. The dose-response of cytotoxic and non-cytotoxic retinal agents was determined using CellTiter-Glo® 3D ATP assay.
Service overview Close Open

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.

Assay design
Models

Retinal organoids with photoreceptors (cone and rod), retinal ganglion cells, horizontal cells and amacrine cells (WT).

Generation of Gene-edited lines available

Assay format

96-well plates (retinal organoids)

Species

Human

Assay readout
  • Cell viability assay (ATP depletion assay, LDH release and microscopy)
  • Qualitative immunofluorescence with cell specific markers & apoptosis markers
  • Gene expression profile of key marker gene by RT-qPCR
  • Microscopy: 2D-TEM and SEM
Time points and replicates
  • Retinal organoids available at D60, D120, D150, D150 & D210 of differentiation
  • Data points are usually performed in triplicates or quadruples with a minimum of 10 organoids.

Models to choose from for this service

Retinal organoids

The retinal organoids are iPSC-derived, and they recapitulate the complex structure of the human retina with laminar cell organisation mimicking embryonic development. They contain the outer photoreceptor segment of the retina that responds to light.

Find out more
A microscope image of retinal organoids
Cone photoreceptor cells labelled with anti-Opsin (Red/Green) antibody.

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