Advanced Human Stem Cell-Derived Macula Models to Counteract Blindness

• Applicant: Professor Dr. Volker Busskamp
• Subject Area: Ophthalmology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 561037818

Age-related macular degeneration (AMD, in the elderly) and Stargardt's disease (STGD, in juveniles) are the most common degenerative macular diseases, cumulatively affecting over 200 million patients worldwide. Deterioration of central vision is incurable, resulting in physical and emotional difficulties and a significant socioeconomic burden. Traditionally, developing treatments for these diseases has relied heavily on animal testing, including rodents, pigs, dogs, and non-human primates (NHPs). However, these animal models do not accurately reflect human conditions. For instance, rodents lack a cone photoreceptor-enriched macula, while NHPs do not typically develop AMD. Current macular organoid in vitro models are limited by long culture duration, difficulty in large-scale production, low reproducibility, and lack of the unique and correct architecture of the retinal pigment epithelium (RPE) with overlaying columnar organization of cone photoreceptors and supporting Müller glial cells required for macular disease modeling. Our main goal is to create a novel, robust, and applicable in vitro model of the human macula that includes the RPE, cone photoreceptors, and supporting Müller glial cells, mimicking their natural 3D architecture. This new system will complement existing animal models, be user-friendly, and could be adopted by multiple investigators to represent the human macula better while reducing animal use. To achieve this goal, we will use human induced pluripotent stem cells (hiPSCs) from genetically defined AMD and STGD patients, as well as from healthy individuals, to obtain the necessary macular cell types. The pre-differentiated macular cells will be stored as ready-to-use components to reduce variability and culture time for tissue engineering. The macular models will be generated by cell printing within novel, optimized bioengineered composite hydrogels to serve as cell-type-specific mimics of the extracellular matrices, thereby providing the cells with appropriate mechano- and bio-sensing signals for adequate polarization and maturation. The composite peptide-polysaccharide-based hydrogels will be fabricated to present the mechanical and bio-active properties specifically required for each cell type. These patient-derived macular testbeds will be used to study macular pathologies as well as to comprehensively develop precise therapeutic interventions. Ultimately, our goal is to achieve high-throughput drug screening readiness, which will allow health technology developers to screen large drug libraries and accelerate drug discovery for preventing blindness. Moreover, our project may lead to the development of macular sheet implants for cell transplantation therapy.

• DFG Programme: Research Grants
• International Connection: Israel
• Partner Organisation: The Israel Science Foundation
• Cooperation Partners: Professorin Lihi Adler-Abramovich, Ph.D.; Professor Ygal Rotenstreich