Purchase this article with an account.
Bar Nachmani, Timothy A Blenkinsop; SEAM Organoids Model Iris Muscle Cell Development from the Optic Cup. Invest. Ophthalmol. Vis. Sci. 2018;59(9):318.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The retinal-pigmented epithelium (RPE) transdifferentiate into myocontractile-like tissue in Proliferative vitreoretinopathy (PVR). In development, among other cell types, the optic cup differentiates into RPE, the neural retina and smooth muscle cells of the pupillary margin. Therefore, during normal development optic cup cells must possess an epigenetic landscape whereby epithelial, neural and myogenic programs are accessible, after which, changes in the epigenetic landscape are made to prevent activating these programs aberrantly. Since RPE transition towards a myogenic lineage in PVR, these programs are reactivated, indicating they are not irreversibly repressed, but likely poised. For this reason, understanding how the epigenetic landscape changes in the developing optic cup may provide insight into how RPE contribute to PVR. We hypothesize that RPE in PVR follow the programs that allow for neuroectoderm-to smooth muscle transition during development.
To understand neuroectoderm plasticity, we differentiated hESCs into previously identified Self-Formed Ectodermal Autonomous Multi-zone of ocular cells (SEAM) structures. We examined whether iris muscle cells developed by qPCR, immunohistochemistry, and phase contrast imaging. We fixed the structures as well as isolated RNA after 3 to 5 weeks of differentiation.
After 30 days of differentiation we evaluated the presence of muscle cells proximal to optic cup lineages. We identified specific lineages in which high PAX6 levels and αSMA are co-localized, suggesting regions of iris muscle development not previously described. These regions often reside near optic cup-derived tissues, resembling iris muscle development from the optic cup lip in embryogenesis. We are now examining the epigenetic changes occurring during iris muscle development.
We have identified a αSMA positive cell population within SEAM organoids, localized at the predicted iris specification region in the optic cup. Further studies will explore iris muscle fate specification and activation of the muscle program alongside RPE muscle cell program suppression. Understanding the players that allow neuroectoderm transition into muscle tissue may also elucidate pathways involved in PVR, which may lead to the discovery of novel therapeutic targets.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
This PDF is available to Subscribers Only