Kruczek, K; (2017) Differentiation and transplantation of mouse embryonic stem cell-derived cone photoreceptor precursors. Doctoral thesis , UCL (University College London).

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Abstract

Daytime vision is highly dependent on cone photoreceptors and retinal degenerations resulting in their death are a leading cause of blindness. A promising treatment strategy is the replacement of lost cones by cell therapy. Here we characterise cone differentiation in retinae derived from suspension cultures of mouse embryonic stem cells (mESCs). Similar to in vivo development, a temporal pattern of progenitor marker expression is followed by the differentiation of early thyroid hormone receptor β2-positive cone precursors and at later stages of culture, photoreceptors exhibiting cone-specific phototransduction-related proteins. We also established that the Notch pathway limits cone genesis, whilst retinoic acid signalling regulates their maturation comparable to their actions in vivo. Importantly, mESC-derived cones can be isolated in large numbers and transplanted into the adult mouse retina. Following transplantation, these cells show the capacity to survive and express mature markers. Together, this work identifies a robust renewable source of transplantable cone precursors for daylight vision repair studies.

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