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Studies in the differentiation and survival of mammalian rod photoreceptors

Neophytou, Constantinos; (1997) Studies in the differentiation and survival of mammalian rod photoreceptors. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

This thesis examines the cell-cell interactions that regulate mammalian rod photoreceptor (rod) differentiation and survival. Rods constitute more than 70% of the cells in the adult rodent retina, which makes them an attractive cell type to study as regards the factors that influence cell fate choice and differentiation, especially as rhodopsin can be used as an unambiguous marker of differentiated rods. I began with an attempt to understand why rods fail to develop in dissociated-cell cultures of neonatal rodent neural retina even when cultured at high density. I have shown that foetal calf serum (FCS) in these cultures arrests rod differentiation at a postmitotic, pre-rod stage of development. In exploring the mechanism by which serum exerts this effect, I have discovered an inhibitory interaction between Muller glial cells and pre-rod cells, which is mediated by leukaemia inhibitory factor (LIF). The inhibitory effect of LIF may help explain why there is a long delay, both in vivo and in vitro, between when precursor cells stop dividing and when they first express rhodopsin. There is evidence that the death of rods in retinitis pigmentosa in rodents occurs by programmed cell death (PCD). I have been able to purify rods by a single step, using a discontinuous Percoll gradient. I am using these purified rods to study the influence of tissue culture extracts, cell culture supernatants, and known signalling molecules on rod cell survival. Factors that save rods in this assay may be useful in the treatment and prevention of retinitis pigmentosa in humans.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Studies in the differentiation and survival of mammalian rod photoreceptors
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Photoreceptors
URI: https://discovery.ucl.ac.uk/id/eprint/10101934
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