Smart, MJK; (2014) A comparative study of the potential for human retinal pigment epithelium utilising an embryonic chick model of the phenomenon. Doctoral thesis , UCL (University College London).

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Abstract

The retinal pigment epithelial (RPE) cells of several species, including: chicken, rat, mouse and newt, have been observed to undergo a phenomenon known as transdifferentiation. This involves the re-specification of the RPE phenotype towards a neuroretinal, or lens phenotype, in response to various cues, including basic fibroblast growth factor (bFGF). Transdifferentiation has yet to be described in human RPE cells, however, this investigation has demonstrated that human cells, including primary fetal, and human embryonic stem cell-derived (HESC), RPE, may retain the capacity to undergo some level of bFGF-mediated transdifferentiation. It appears that the process is likely comparable to that observed in the embryonic chick model of the phenomenon, given that human transdifferentiation appears to be restricted to the earliest stages of RPE development (approximately 6 weeks). Additionally, the features of transdifferentiated RPE observed in the earliest available human tissue are shown to resemble that of a similar stage in chick development (HH27), which is shown to display limited transdifferentiation for the first time, in contrast with previous studies which report the loss of potential for transdifferentiation at this stage. It remains unclear as to why RPE cells lose the capacity for transdifferentiation with development, however, it appears to be linked to, but not exclusively a result of, a loss in the expression of Pax6 across the RPE monolayer, given both capacity for transdifferentiation, and Pax6 expression, are both variable in different regions of the same monolayer, in the chick model of transdifferentiation. Known RPE augmentation signaling pathways, including bone morphogenic protein (BMP) and Sonic hedgehog (Shh) were analysed for their potential involvement in the restriction of transdifferentiation, however, neither appeared to be directly involved. Further studies in the embryonic chick model of the phenomenon will be necessary to unlock this potential in human RPE cells.

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