Exploring retinal AD phenotypes using human pluripotent stem cell‐derived retinal organoids

• Published in: Alzheimer's & dementia Vol. 17; pp. e054171 - n/a
• Main Authors: Lavekar, Sailee Sham, Gomes, Catia S, Huang, Kang‐Chieh S, Iglesias, Clara S, Meyer, Jason S.
• Format: Journal Article
• Language: English
• Published: United States 01.12.2021
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.054171

Background AD‐relevant phenotypes include an accumulation of Aβ plaques and neurofibrillary tangles, yet the identification of these features in the human patient brain is difficult due to expensive or invasive methods. As the retina is considered a window into the central nervous system, it may provide an opportunity for screening the progression of AD phenotypes. Thus, the goal of this project was to explore the use of human pluripotent stem cell (hPSC)‐derived retinal organoids as an in vitro model of retinal AD phenotypes. Method Control and familial AD (PSEN1‐A246E) hPSCs were used for all studies. Initially, the ability of fAD hPSCs to give rise to retinal organoids similarly to control hPSCs was explored. Subsequently, the onset of AD‐relevant phenotypes, including the Aβ42:Aβ40 ratio as a biomarker of AD, was analyzed by ELISA using conditioned medium derived from PSEN1 and control retinal organoids. Ongoing experiments are analyzing additional AD features within retinal organoids. Result Retinal organoids were efficiently differentiated from both control and PSEN1 cell lines. Upon maturation, the Aβ42:Aβ40 ratio was increased in the conditioned medium derived from PSEN1 retinal organoids as compared to controls. These results support the use of retinal organoids as a model system for analyzing retinal phenotypes in AD. Conclusion hPSC‐derived retinal organoids can effectively exhibit AD‐related phenotypes when differentiated from patient‐derived samples with the PSEN1 SNP. Therefore, the ability exists to further identify cellular features of the disease state that can be eventually developed as early biomarkers in the eye as a window into the central nervous system.