Hasan, S.M.; (2008) Characterisation of immortalised human foetal retinal progenitor cell lines. Doctoral thesis , University of London.

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Abstract

Inherited retinal dystrophies and age-related macular degeneration (AMD) are leading causes of blindness. Current treatments only slow disease progression in a minority of patients, therefore it is important to develop new treatments that can regenerate lost cells, restore retinal function and halt disease progression. Retinal progenitor cells have the potential to replace degenerating photoreceptors in retinal diseases. This thesis explores the viability of using immortalised human foetal retinal progenitor cells for this purpose, and aims to elucidate the trophic factors required, in vitro, to drive these cells towards retinal cell lineages. We also examine their potential to survive, integrate and differentiate in the diseased and developing rat retina. Two human foetal retinal progenitor cell lines were established by infecting retinal foetal tissue with the temperature-sensitive tsT-SV40 antigen. The immortalised progenitor cells were compared to primary human foetal retinal progenitor cultures, and both were shown to express similar markers of neural progenitor cells and early neuronal cell types. Several trophic factors were investigated, including serum, retinoic acid and conditioned medium, with respect to their ability to influence gene expression. Serum appeared to induce expression of ganglion cell markers, and conditioned medium stimulated cell proliferation. Cells were also grafted into neonatal hooded Lister rats and RCS dystrophic rats, and neither the primary nor the immortalised progenitor cells demonstrated integration into the retina. In the RCS rat, cells were engulfed by host macrophage/microglia and showed no signs of integration or expression of neuronal markers. Immortalised cells, in vivo, stained positively for Ki67 and low levels of nestin, but exhibited limited ability to differentiate or integrate. These data indicate that immortalised progenitor cells maintain many characterisics of unimmortalised progenitor cells, and suggest that immortalisation of retinal progenitors may have long term therapeutic possibilities.

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