Retinal Organoid

Overview of Retina

The retina, an integral part of the central nervous system (CNS), consists of seven different cell types, histologically organized in an evolutionarily conserved laminar structure, which are responsible for generating and transmitting the visual signal. For example, rod and cone photoreceptors (rods and cones, respectively) capture light reflected from an object and generate an electrical signal. This is subsequently relayed to retinal ganglion cells (RGCs) for transmission to higher centers in the brain for visual perception after having been modulated by the intervening neurons, the horizontal cells (HCs), bipolar cells (BCs), and amacrine cells (ACs). Müller glia (MG), the single glia generated by the multipotential retinal progenitor cells (RPCs), regulates the homeostasis of this highly metabolically active and energy-demanding tissue. The non-neuronal retinal pigment epithelium (RPE), located outside the retina, yet in intimate contact with photoreceptors, plays a critical role in the structural and functional viability of these cells.

Fig.1 Schematic overview of in vivo and ex vivo approaches to regenerative medicine through recapitulating developmental mechanisms.¹

Fig. 2. Summary of potential applications of retinal organoids.²

Services at Creative Biolabs

With years of experience devoted to neuroscience, Creative Biolabs has accumulated extensive expertise. We have developed a comprehensive technology platform focusing on custom brain organoids including retinal organoids. Our platform is equipped with the latest technologies, advanced facilities, and experienced experts. All of these consist of strong guarantees of the qualities of our services.

If you are interested in custom retinal organoid services, or any other custom brain organoids services, please don't hesitate to contact us for more information.

Our procedure begins with the propagation of hiPSCs under conditions that stimulate retinal differentiation. Using defined factors and growth conditions, the cells are differentiated into RPCs. These cells undergo further differentiation and maturation to give rise to an array of retinal cell types in an organoid structure.

• Our service provides the benefits of advanced technologies and expertise in retinal differentiation. We ensure that the retinal organoids generated contain all major cell types, including retinal ganglion cells, photoreceptors, and RPE cells while maintaining the structural and functional properties.
• Our advanced imaging techniques, comprising immunocytochemistry, confocal microscopy, electron microscopy, etc., are utilized for the confirmation of generated retinal cell types as well as assessing the cellular organization within the organoids.
• Additionally, we offer extra services like detailed phenotypic analysis, functional assessment using electrophysiological techniques, and compound screening for drug discovery and development.

Our retinal organoid development service is ideal for researchers studying retinal development, disease modeling, drug discovery, and therapeutic development. It would prove pivotal in research areas requiring a platform that closely replicates human retinal tissue in vitro, such as AMD, retinitis pigmentosa, and other retinal degenerative diseases. We also offer flexibility in our services, including but not limited to:

Published Data

Jackie L. Norrie, et al. developed a laboratory model of human retinoblastoma formation. iPSCs were prepared from 15 participants with germline RB1 mutations. Each stem cell line was validated, characterized, and then differentiated into the retina using a 3-dimensional organoid culture system. The original Sasai method and the modified 3D-RET protocol were used to produce 3D retinal organoids.

The results showed that retinal organoid quality was similar between the retinal organoids generated using the H9 ESC lines and the iPSC lines generated from participants with germline RB1 alterations, but the 3D-RET protocol generated iPSC lines with increased retinal organoid efficiency as well as more homogeneous and consistent organoid sizes and shapes.

Fig. 3 Drawing of the steps in the Sasai and 3D-RET retinal organoid protocol.³

Application of Retinal Organoid in Diseases

The loss of the visual signal when photoreceptors degenerate in age-related macular degeneration (AMD) or retinitis pigmentosa (RP) or the lost ability to transmit it to the brain when RGCs degenerate in glaucoma invariably leads to blindness. Unfortunately, there is no effective treatment to reverse the loss of vision when photoreceptors or RGCs die. However, transformative research over the last twenty years has led to discoveries that are promising for regenerative medicine for retinal degeneration: self-organization of pluripotent stem cells into 3D retinal organoids, providing platforms for disease modeling and cells for retinal repair. When combined with drug screening, disease modeling using iPSC lines from patients of different genetic backgrounds with retinal degeneration of familial and sporadic origins has the potential for (1) clinical trial in a dish, the depth and breadth of which is not fully achievable in regular clinical trials, and (2) prospectively selecting patients for personalized treatment. These findings suggest that strategies could be formulated for practical and personalized regenerative medicine with the purpose of recovering and preventing vision loss due to degenerative changes in diverse populations of patients.

FAQs

Q: Can you provide examples of how your retinal organoids have been used in previous research studies?

A: Our retinal organoids have been successfully used in various research studies to investigate retinal disease mechanisms, screen potential drug candidates, and explore gene therapy approaches. For instance, they have been employed to model the degenerative processes in AMD, study the genetic mutations causing RP, and test the efficacy of CRISPR-based gene editing techniques in restoring retinal function. These examples highlight the versatility and impact of our organoids in advancing retinal research.

Q: Are there any specific handling or storage requirements for the retinal organoids once they are delivered?

A: Yes, there are specific handling and storage requirements to maintain the viability and functionality of the retinal organoids upon delivery. We provide detailed protocols outlining the recommended storage conditions, typically involving immediate transfer to a controlled environment such as a cell culture incubator. Additionally, guidelines for medium changes, feeding schedules, and handling techniques are included to ensure optimal maintenance and experimental success.

Q: Will the retinal organoids provided be consistent in quality?

A: Yes, we strive to ensure that every batch of retinal organoids we produce and deliver to our customers is of the highest and consistent quality. We achieve this through our stringent methodology and precise formulations in the development process.

Q: Can you customize the retinal organoids to meet specific research needs?

A: Yes, we offer customization options for our retinal organoid development service. Depending on your research requirements, we can modify the differentiation protocol, incorporate specific genetic modifications, or provide organoids at various developmental stages. This flexibility allows us to tailor the organoids to better suit your experimental objectives and ensure the best possible outcomes for your research.

Scientific Resources

Emerging Tools for the Study of Neurological Diseases - Brain Organoids

References

1. Ahmad, I., et al. Recapitulating developmental mechanisms for retinal regeneration. Prog Retin Eye Res. 2020, 76: 100824.
2. Llonch, S., et al. Organoid technology for retinal repair. Dev Biol. 2018, 433(2): 132-143.
3. Norrie, Jackie L., et al. "Retinoblastoma from human stem cell-derived retinal organoids." Nature Communications 12.1 (2021): 4535.

For Research Use Only. Not For Clinical Use.