Retinal Organoid Modeling Service

The human retina, a complex and exquisitely organized neural tissue, is responsible for capturing light and initiating the process of vision. Degenerative diseases affecting the retina, such as inherited retinal dystrophies (IRDs), age-related macular degeneration (AMD), and glaucoma, are leading causes of irreversible blindness worldwide, creating a significant unmet medical need. Translating potential therapies from preclinical studies to clinical success remains challenging, often hindered by limitations of traditional 2D cell cultures and species differences in animal models.

Progressing new treatments for retinal diseases often stalls because standard lab models don't fully capture human biology. Creative Biolabs offers a solution with our Retinal Organoid Modeling Services. By cultivating 3D retinal organoids (hROs) from human iPSCs, we create models that replicate key features of human retinal development and structure in vitro. This approach provides a genuinely human-based system for exploring disease pathways, testing potential therapies, and evaluating safety.

Our Human Retinal Organoid Platform

Our hROs are generated using robust, optimized protocols, potentially employing serum-free and xeno-free conditions suitable for clinical translation. Starting from well-characterized human iPSCs (healthy donor or patient-derived), we guide differentiation through stages mimicking embryonic eye development, resulting in self-organizing 3D structures.

Key features of our hRO platform include:

• Complex Cellular Composition: Our organoids contain the major classes of retinal neurons (photoreceptors – rods and cones, retinal ganglion cells, bipolar cells, amacrine cells, horizontal cells) and Müller glia, arranged in a distinct laminar architecture resembling the native human retina.
• Highly Reproducible & Efficient: Our optimized platform ensures highly reproducible retinal organoid generation with consistent results batch-to-batch. Its high efficiency supports robust, large-scale production suitable for high-throughput applications.
• Structural Maturation: We achieve significant maturation, including the development of photoreceptor inner and outer segment-like structures critical for light detection. Retinal pigment epithelium (RPE) can also be generated, often from the same iPSC source, for co-culture studies.
• Functional Activity: Our hROs exhibit functional characteristics, including responses to light stimuli and pharmacological agents, assessable via advanced electrophysiological and imaging techniques.

Fig.1 Generation of retinal organoids.¹

Comprehensive Retinal Organoid Services

We offer a flexible suite of services designed to accelerate your vision research:

1. Retinal Organoid Generation:

• Custom generation of hROs from your iPSC lines or our characterized control/patient-derived lines.
• Scalable production using optimized protocols (e.g., microwell-based or adherent culture methods).
• Delivery at specific developmental time points (e.g., Day 60 for RGC enrichment, Day 150+ for mature photoreceptors) tailored to your research focus.
• Option for cryopreserved organoids or dissociated cells for flexible experimental planning.
• Generation of iPSC-derived Retinal Pigment Epithelium (RPE) for barrier function studies or co-culture models.

2. In-Depth Characterization:

• Molecular Profiling: Understand the cellular makeup and developmental stage of your organoids through bulk, mapping gene expression patterns across diverse retinal cell types.
• Structural & Cellular Analysis (IHC/Imaging): Confirm correct retinal architecture and cell placement using high-resolution confocal microscopy combined with multiplex immunofluorescence staining for essential protein markers within the distinct retinal layers.
• Ultrastructural Examination (TEM): Verify advanced cellular maturity by examining fine details, such as the formation of photoreceptor outer segments or synaptic structures, with Transmission Electron Microscopy.
• Functional Assessment: Test the physiological responsiveness and network capabilities of the organoids via calcium imaging to capture responses to light or drug application, alongside multi-electrode array (MEA) or patch-clamp recordings to analyze neural activity patterns.

3. Disease Modeling:

• Patient-Specific Retinal Disease Models: Generate hROs using iPSCs derived directly from patients with specific inherited retinal conditions (including Retinitis Pigmentosa, Stargardt disease, LCA, and others) to study individual disease phenotypes in vitro.
• Precision Genetic Modeling (CRISPR/Cas9): Leverage gene editing to either introduce known disease-causing mutations into healthy control iPSC lines or correct genetic defects in patient-derived cells, creating valuable isogenic pairs for direct comparison.
• Modeling Complex Retinopathies: Study cellular pathologies relevant to complex conditions like Age-Related Macular Degeneration (AMD) or glaucoma by examining specific features like RPE dysfunction or RGC loss within the 3D organoid system.

4. Drug Discovery & Toxicology:

• Compound efficacy screening using functional readouts (e.g., neuroprotection assays, visual function surrogates).
• Retinal toxicity evaluation using standardized assays (e.g., ATP/LDH for viability) and functional endpoints.
• High-throughput screening (HTS)-compatible formats (e.g., 96-well plates) for rapid assessment of large compound libraries.
• Mechanism-of-action studies for lead compounds.

5. Gene Therapy Evaluation:

• Assessment of Adeno-Associated Virus (AAV) vector performance, including tropism for specific retinal cell types, transduction efficiency, and transgene expression analysis.
• In vitro evaluation of the efficacy and safety of novel gene therapy strategies prior to in vivo testing.

6. Custom Development:

• Collaborative development of tailored organoid models or assays to meet specific research objectives.
• Establishment of advanced co-culture systems (e.g., RO-RPE, vascularized organoids).

Key Applications

Our Retinal Organoid Modeling Services empower breakthroughs across numerous areas:

• Inherited Retinal Disease Research (RP, LCA, Stargardt, etc.)
• Age-Related Macular Degeneration (AMD) Modeling
• Glaucoma Research (RGC Survival)
• Ocular Drug Discovery & Development
• Retinal Toxicology & Safety Assessment
• Gene Therapy Vector Development & Validation
• Human Retinal Development Studies
• Cell Therapy Source Characterization

Our Streamlined Project Workflow

Accelerate your vision research using the most advanced, human-relevant in vitro models available. Partner with Creative Biolabs to leverage the power of retinal organoids.

Reference

1. Lu, Tian et al. "Decoding transcriptional identity in developing human sensory neurons and organoid modeling." Cell vol. 187,26 (2024): 7374-7393.e28. doi:10.1016/j.cell.2024.10.023. Distributed under Open Access License CC BY 4.0 without modification.