Anatomy and Neuroscience - Theses
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ItemThe condition of the retina in retinitis pigmentosa during late stages of degeneration( 2012)Retinitis pigmentosa (RP) is a family of inherited retinal degenerations that are characterised by photoreceptor death resulting in blindness. It was once thought that following photoreceptor death, the inner retina remained unchanged. However, studies have begun to show that there are extensive changes at late stages in the disease process. This thesis further extends these studies by examining the inner retina at various time points after photoreceptor death so that the cellular changes that arise throughout the degenerative process can be characterised. A novel transgenic mouse model, the rd1-FTL, was used to document the condition of the retina. This animal model expresses a mutation which results in retinal degeneration as well as containing an axonal targeted transgenic marker gene that labels all neurons that have the c-fos gene activated. A combination of enzyme histochemistry and fluorescence immunohistochemistry was used to reveal an up-regulation of c-fos in the central retina following complete photoreceptor loss that remained throughout the later stages of degeneration. This was also coupled with a major glial dysfunction in this area. Neurochemical analysis prior to and during c-fos upregulation revealed significant changes in the inner retina. Amino acid immunocytochemistry was used to show that many amino acids in the degenerated retina were altered in patches across the retina. The most significant changes were documented in Müller cells and bipolar cells. Additionally, gross remodelling of neural and glial cells occurred in the retina which worsened as animals aged. A comprehensive morphological analysis of retinal ganglion cells in the degenerated retina showed that the cell types which covered the largest area in the retina were altered whilst the smaller cells types remained unchanged. However, these smaller cells did show altered morphology in regions that also expressed c-fos in late stages of degeneration. Furthermore, there were significant changes in the stratification of many ganglion cells in the degenerated retina that included the loss of certain cell types as well as different branching patterns of dendrites. Overall, this thesis shows that there are extensive changes in the inner retina following photoreceptor loss. It provides a thorough examination at different stages in the degenerative process to highlight the varying conditions that can occur in this disease. Approaches aimed at vision restoration rely on a strong understanding of this underlying cellular anatomy and this work will assist with the design of these approaches.