Related Experiment Video
Updated: Mar 6, 2026
Reconstruct Human Retinoblastoma In Vitro
Published on: October 11, 2022
Retinoblastoma: unveiling molecular pathogenesis and pioneering organoid-driven therapeutic innovations
1Department of Ophthalmology, The Affiliated Yongchuan Hospital of Chongqing Medical University, Yongchuan District, Chongqing, 402160, People's Republic of China. 2022220507@stu.cqmu.edu.cn.
Abstract:
Retinoblastoma (RB), which is the most common pediatric intraocular malignancy driven by RB1 inactivation, presents with clinical challenges, such as treatment toxicity, relapse, and resistance. Traditional models inadequately replicate human RB genetics or tumor heterogeneity, warranting the development of advanced in vitro platforms. Retinal organoids generated from human pluripotent or patient-specific stem cells enable three-dimensional(3D) modeling of the tumor microenvironment, drug screening, and mechanistic studies. This review summarizes RB pathogenesis, including RB1 loss, MYCN amplification, epigenetic dysregulation (e.g., METTL3-mediated m6A), and dysregulated pathways (PI3K/AKT/mTOR, Hedgehog), and highlights CRISPR-engineered organoids for identifying cone precursors as tumor origins and validating therapies (CDK4/6 inhibitors and sunitinib). Despite these advances, organoid applications are limited by high costs, variable success rates, incomplete immune/vascular mimicry, and limited scalability. Current microfluidic systems partially address vascularization but lack functional perfusion. Future efforts should integrate multiomics, refine vascularization via 3D bioprinting, and develop immunocompetent models to address the disparity between preclinical research and clinical application. Organoid technology has the potential to advance personalized therapies and ultimately enhance the survival and quality of life of patients with RB worldwide.
Insights
Retinal organoids offer advanced 3D models for studying retinoblastoma (RB) pathogenesis and testing therapies. Future organoid development aims to improve personalized treatments and patient outcomes for this pediatric eye cancer.
Area of Science:
- Ophthalmology
- Developmental Biology
- Cancer Research
Background:
- Retinoblastoma (RB) is a common pediatric intraocular malignancy driven by RB1 inactivation, posing treatment challenges like toxicity, relapse, and resistance.
- Existing models fail to fully replicate human RB genetics and tumor heterogeneity, necessitating improved in vitro platforms.
Purpose of the Study:
- To review retinoblastoma pathogenesis, including genetic and epigenetic factors.
- To highlight the application of retinal organoids and CRISPR-engineered models in studying RB.
- To discuss the limitations and future directions of organoid technology for RB research.
Main Methods:
- Review of existing literature on retinoblastoma pathogenesis and modeling.
- Focus on retinal organoids derived from human pluripotent or patient-specific stem cells.
- Discussion of CRISPR-engineered organoids for identifying tumor origins and validating therapies.
Main Results:
- Retinal organoids provide a 3D model for the tumor microenvironment, enabling drug screening and mechanistic studies.
- CRISPR-engineered organoids have identified cone precursors as potential tumor origins and validated therapies like CDK4/6 inhibitors and sunitinib.
- Key RB pathogenesis factors include RB1 loss, MYCN amplification, METTL3-mediated m6A epigenetic dysregulation, and aberrant PI3K/AKT/mTOR and Hedgehog pathways.
Conclusions:
- Organoid technology offers significant potential for advancing personalized therapies for retinoblastoma.
- Limitations such as cost, variability, and incomplete mimicry of physiological systems need to be addressed.
- Future research should focus on integrating multiomics, improving vascularization through 3D bioprinting, and developing immunocompetent models to bridge the gap between preclinical findings and clinical application.
