Battlefield retinal laser injury is an infrequent but potentially devastating cause of irreversible blindness. Resultant laser-induced photoreceptor death may occur by necrosis or apoptosis, the latter which is a form of programmed cell death that may be physiological or pathological. Though necrosis cannot be prevented, apoptosis may be inhibited under certain conditions. Therefore, following retinal laser injury, specific treatment aims to target apoptotic photoreceptors and may take the form of neuroprotection or cell replacement. The primary aim of this thesis was to construct an in vivo model in which to observe the effects of retinal laser exposure on cone photoreceptor apoptosis. Current methodology to determine the effects involves histological techniques and is therefore limited to being cross-sectional. An in vivo model would permit longitudinal study to observe the cone response to injury using clinically relevant applications, including fundus autofluorescence imaging. Such a construct would enable more sensitive evaluation of new therapies which would be of direct translational relevance. The secondary aim was to investigate potential therapeutic options for retinal laser injury by pharmacological means in the form of CNTF or cell transplantation. To identify the possible molecular signals involved in neurotrophic factor-induced photoreceptor cell survival, apoptotic gene expression was investigated focusing on those genes modulated by the CNTF pathway.

After over a decade of its discovery, the Electroretinogram (ERG) still remains the objective tool that is conventionally used in assessment of retinal function in health and disease. Although there is ongoing research in developing ERG recording techniques, interpretation and clinical applications, there is still a limited understanding on how each photoreceptor class contribute to the ERG waveform and their role and/or susceptibilities in various retinal diseases still remains unclear. Another limitation with currently used conventional testing protocols in a clinical setting is the requirement of an adaptation period which is time consuming. Furthermore, the ERG responses derived in this manner are recorded under different stimulus conditions, thus, making comparison of these signals difficult. To address these issues and develop a new testing method, we employed silent substitution paradigm in obtaining cone- and rod- isolating ERGs using sine- and square- wave temporal profiles. The ERGs achieved in this manner were shown to be photoreceptor-selective. Furthermore, these responses did not only provide the functional index of photoreceptors but their contributions to their successive postreceptoral pathways. We believe that the substitution stimuli used in this thesis could be a valuable tool in functional assessment of individual photoreceptor classes in normal and pathological conditions. Furthermore, we speculate that this method of cone/rod activity isolation could possibly be used in developing faster and efficient photoreceptor-selective testing protocols without the need of adaptation. / Bradford School of Optometry and Vision Sciences scholarship

The overall objective of this thesis was to understand better the mechanisms that shape the diversity in colour vision of fish, and to explore the adaptive significance of this divergence. Among the vertebrates, teleost fish show the greatest diversity in colour vision systems. The cichlid model system illustrates that the visual system of fish may differ among species, sexes, individuals, and life stages of individuals. The large number of available cone opsin genes, which have resulted from multiple opsin gene duplications, facilitates this high degree of variation in the mechanisms of colour vision. In general, cichlids possessed complements of four to five cone pigments, and these complements varied across species, sexes, and individuals. Additionally, lens transmission, cone pigment expression, post-receptoral sensitivity, and retinal circuitry differed across life stages of individuals. My results suggest that the diversification of colour vision across species and across life stages of individuals contributes to sensory adaptations that enhance both the contrast of zooplanktonic prey, and the detection of optical signals from conspecifics. Therefore, both natural and sexual selection may have worked in concert to shape colour vision in fish. Since light is more complex under water than on land, fish required four to six cone classes to reconstruct the colour signals reflected from aquatic objects. This suggests that the large number of cone pigments in fish have likely evolved to enhance the reconstruction of the complex colour-signals in aquatic environments. Taken together, these findings improve our understanding of the variable nature of fish colour vision, and, more generally, help unravel the evolution of photoreceptors and colour vision. / Thesis (Ph.D, Biology) -- Queen's University, 2012-05-14 13:16:50.276