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New Eye-on-Chip models from Amsterdam UMC

Posted on by hDMT

The team of Prof Arthur Bergen, department of Human Genetics, Amsterdam UMC, has recently developed various human retina-on-a-chip models.These models represent a number of genetically determined eye diseases, such as age-related macula degeneration, glaucoma and retinitis pigmentosa. Next to WT models (Figure 1) , we have developed a number of CRISPR/Cas9 knock-out and iPSC-derived patient organoids (not shown) and a new class of biosynthetic organoids (Figure 2). Obviously, such models are essential for deep understanding of human eye development and disease pathology and to develop or test emerging therapies. According to recent international patient surveys, vision disorders reduce the quality of life comparable to Alzheimer’s disease and some forms of cancer. Finally, we also reduce the experimental need for otherwise essential animal models.

 

Legend Figure 1: Various WT retinal organoids, to serve specific purposes. The pictures above (L to R): (L): a (stained section from an) embryoid body developing into a retinal organoid showing a number of retinal cell layers. (M) a fully developed 3D WT human retinal organoid, including functional photoreceptors on the outside, inner cell layers underneath and an inner cell mass; (R) outgrowth of ganglion cell axons from a WT retinal organoid, representing a model for retinal, optic nerve and neurodegenerative disorders (Pictures: Philip Wagstaff 2021; partly unpublished).

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Legend to Figure 2: 3-D cellular bioprinting of a new prototype model-in-a-dish for Age-related Macula Degeneration and the outer retina-blood barrier. (a) Impression cellular bioprinter installed at Bergen lab at Amsterdam UMC; (b) Top overview and (c) confocal microscopy: details of 3D reconstruction of the model after printing and cellular growth. (b and c): Defined Deposits (violet) and Retinal Pigment Epithelial cells (represented by blue nuclear DAPI staining) are printed on a solid support (Pictures recently presented on annual Neuroscience meeting Amsterdam: Estzer Emri, 2021)

Philip E. Wagstaff, Anneloor L. M. A. ten Asbroek, Jacoline B. ten Brink, Nomdo M. Jansonius & Arthur A. Bergen (2021) An alternative approach to produce versatile retinal organoids with accelerated ganglion cell development. Scientific Reports volume 11, Article number: 1101 (PMID: 33441707)

Arthur A. Bergen, Swati Aryad, Céline Koster, Matthew G.Pilgrim, Dagmara Wiatrek-Moumoulidis, Peter J. van der Spek, Stefanie M. Hauck, Camiel J.F. Boon, Eszter Emri, Alan J. Stewart, Imre Lengyel (2019) On the origin of human proteins in drusen (in age-related macular degeneration): the Meet, Greet and Stick hypothesis. Progress in Retin and Eye Res 70, Pages 55-84 (PMID: 30572124)

Sarah F Janssen, Theo GMF Gorgels, Wishal D Ramdas, Caroline CW Klaver, Cornelia M van Duijn, Nomdo M Jansonius, Arthur A Bergen (2013) The vast complexity of primary open angle glaucoma: disease genes, risks, molecular mechanisms and pathobiology. Prog Retin Eye Res 37:31-67 (PMID: 24055863)

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