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Title: Role of visual pigment in primary events leading to retinal dysfunction and development of age-related macular degeneration
Author: Handzel, Kinga Elzbieta
ISNI:       0000 0004 2750 6642
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2010
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The aim of this study was to gain a deeper understanding of the role of the visual pigment in retinal damage and its contribution to initial pathways in the pathogenesis of age-related macular-degeneration (AMD). Initially, the kinetics of all-trans-retinal (ATR) hydrolysis from opsin and its reduction to retinol formation were determined. Based on the results, singlet oxygen generation was investigated as a function of ATR position and the availability of cofactors required for retinol formation. The yield of singlet oxygen generated by ATR increased upon hydrolysis of ATR from opsin and further, upon its release to the disc membrane. The presence of ATP and NADPH did not influence the signals significantly. (Photo)cytotoxicity studies revealed that both ATR and its degradation products (dATR) are toxic to cells, with dATR having a more deleterious effect. Toxic effects of dATR were prevented by a-tocopherol, retinol and phosphatidylethanolamine, whereas none of hydrophilic antioxidants tested exerted a substantial effect. Both ATR and dATR exhibited a similar ability to generate singlet oxygen when excited with visible light, whereas products of ATR degradation were characterised by greater photosensitising properties than ATR for shorter wavelengths. The yield of singlet oxygen for retinol was lower than for ATR in acetone. Although, retinyl ascorbate has a great potential to be a strong singlet oxygen quencher, the difference in the quenching rate was not found to be statistically significant when compared with all-trans-retinol or ascorbyl palmitate. Accumulation of products of rhodopsin bleaching increased the formation of lipofuscin-like inclusion bodies. Exposure of cells to light was associated with higher levels of fluorescence characteristic for oxidised cellular components. In summary, the results suggest that products of visual pigment bleaching may contribute to the toxic effects of light on the retina. In conjunction with published findings, it supports the theory that ATR can play an important role in causing RPE dysfunction as occurring in retinal aging and AMD.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available