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Title: Neuroprotection of cone photoreceptors in retinitis pigmentosa
Author: Lipinski, Daniel Mark
ISNI:       0000 0004 2746 9263
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2013
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Retinitis pigmentosa (RP) is a genetically and phenotypically heterogeneous condition that affects approximately 1 in 4000 individuals worldwide. The most common presentation of RP is a rod-cone dystrophy, where the degeneration of cone photoreceptors occurs secondary to advanced rod loss, leading to a significant decline in central vision and a corresponding reduction in patient quality of life. The mechanisms underlying secondary cone loss are poorly understood, particularly in disorders where the gene defect is unknown or manifest only in rod photoreceptors. Consequently, the thesis presented herein proceeds on several fronts. First, in the long term a greater understanding of the causes underlying cone loss in RP is likely to be beneficial, and so in chapter one a dominant cone degeneration is characterized using intrinsically fluorescent cone photoreceptors to track the degenerative process. Second, as we develop a greater understanding of the genetic etiology underlying RP it is likely that the number of large genes identified as being causative will increase. As currently there is no efficient way to deliver large genes to photoreceptors, chapter two explores the use of alternate viral vectors that might be used to deliver a large therapeutic transgene. Lastly, whilst our understanding of cone loss in RP remains incomplete, it is necessary to develop a broadly applicable therapy to slow or attenuate further cone loss in RP patients regardless of the underlying cause. In chapters three and four we examine the use of low molecular weight "growth factors‟, such as ciliary neurotrophic factor (CNTF), to preserve cone photoreceptors long-term using a rhodopsin knockout model of RP.
Supervisor: MacLaren, Robert E. Sponsor: Fight for Sight UK
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Gene medicine ; Ophthamology ; Viruses ; cone photoreceptor ; gene therapy ; growth factor