Findings by a team at Newcastle University, and published in the academic journal Stem Cells, has identified a new organoid model that encompasses all human retinal cell types and that is responsive to light.
The number of people worldwide affected by visual impairment is huge — currently estimated at 285 million — and continues to rise as life expectancy increases.
Many of those affected by sight problems are older people, suffering from diseases such as age-related macular degeneration (AMD), retinitis pigmentosa (RP), and glaucoma.
Until now, most drug studies aimed at finding treatments for these diseases are performed on rodent models, a situation that is far from ideal due to the fundamental structural and functional differences between a rodent’s and a human’s retina.
Recent studies by other researchers have shown the promise of iPSCs in producing “workable” light-responsive 3D retinal cell models.
To date, however, these organoids have not been used extensively in toxicology or pharmacology screening due largely to the lack of differentiation methods that generate them in numbers large enough for this type of testing.
The Newcastle University team addressed this issue by investigating five separate human iPSC lines to determine their ability to generate such retina.
Majlinda Lako, professor of stem cell sciences at Newcastle University’s Institute for Genetic Medicine, said: “In particular we wanted to gauge the organoids’ capacity for large-scale automation and drug screening as well as their usefulness in toxicity screening programs.”
Three of the five cell lines in the study came from healthy donors, while the other two were from diseased subjects — one with AMD and the other with RP.
Despite this, all five lines generated light-responsive retinal organoids, although they showed significant variability in their overall efficiency to do so.
Additionally, by month five, each organoid produced from the lines responded to light at a level comparable to that recorded in neonatal mice retina close to the time of eye opening.
Professor Lako said: “This variability in the lines’ efficiency cannot be related solely to disease pathology as it was encountered also between iPSC lines from unaffected individuals. Seeding density and nutrient availability seemed to have had the most dominant effect on retinal organoid formation.
“Overall, our study affirms that light-responsive retinal organoids derived from carefully selected and differentiation efficient iPSC lines can be generated at a scale needed for pharmacology and drug screening purposes.”
Through statistical design experiment, the authors determined the optimal application of key growth factors, small molecules and cell seeding density to generate light and drug responsive laminated retinal organoids in a multi well plate format that allows scalability and automation.
Dr Jan Nolta, Editor-in-chief at Stem Cells, said: “We congratulate Professor Lako and her team on the development of light-sensing 3-D organoids containing all human retinal types, which can significantly enhance the development of therapy for blindness.”
Human induced pluripotent stem cells generate light responsive retinal organoids with variable and nutrient dependent efficiency
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