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Matthew J. Smart, Michael B. Powner, Marcus Fruttiger, Peter J. Coffey, Anthony A. Vugler; Retinal Markers In The Developing Human Fetal Retinal Pigment Epithelium. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4104.
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Very little is known about the development of the retinal pigment epithelium (RPE) in the human foetus. In particular, it is not clear to what extent these cells express markers characteristic of adult RPE or neural retina. Here we use an immunohistochemical approach to study protein expression in this important cell type.
Human fetal eyes (ranging from Carnegie stage 18 (CS18) to 12 weeks gestation) were fixed overnight in 4% PFA following post-mortem intervals of up to 6hrs. Retinal sections were immunostained with antibodies raised against a number of different RPE specific / general neural retinal markers. These included the pre-melanosomal marker Pmel17, Bestrophin, RPE65, OTX2, Pax6, Crx, Chx10, Sox2, nestin and the molecular chaperone protein αA-crystallin.
The foetal RPE stained positively for OTX2 and CRX, with some immunoreactivity for bestrophin clearly visible at the youngest stage examined (CS18), We did not observe CRALBP in the RPE at any developmental stage and no clear signal for bestrophin or RPE65 could be detected at the later stages of development. The RPE also appeared negative for nestin, Sox2, Chx10 and Pax6. In contrast, there was robust expression of Pmel17 in the RPE at all stages examined, including CS18 where this layer is only lightly pigmented. Surprisingly, expression of Pmel17 was also seen within the peripheral neural retina. These non-pigmented, Pmel17 positive cells were found to be co-labelled with the neural retinal progenitor markers nestin, Pax6 and Chx10, together with αA-crystallin.
Human foetal RPE at the ages studied here fail to exhibit robust expression of certain RPE-specific markers characteristic of the fully differentiated adult cell type. The co-localization of Pmel17 with neural retinal markers is intriguing and may reflect the shared mutli-potent lineage of RPE and underlying retinoblastic layers. It may also indicate a more complex interaction between the two layers during retinal development. Further studies are necessary to elucidate which of these is the case.
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