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In recent years there has been a great deal of interest in describing the relationships between the structure and function of the retina at a local level. Techniques such as the multifocal electroretinogram (mfERG) provide objective measures of localised retinal function and could provide new information about structure- function comparisons. Novel studies relating mfERGs with eo-localised structure and subjective function information have been undertaken in two ocular conditions, myopia and retinitis pigmentosa (RP). Measurements include peripheral resolution acuity, retinal thickness from optical coherence tomography (OCT), cone counts from confocal scanning laser ophthalmoscopy (CSLO) and ocular length at different eccentricities. In myopia where there is axial elongation of the eye, co-localised loss of mfERG function and reduced retinal cell density occur in regions where retinal laminar structure is thinned. This relationship is more evident in the peripheral retina rather than the central retina. In RP, where chronic deformation of the retina is likely, thinning of the photoreceptor layer and thickening of the inner retinal layers occurs. Only in some regions of the retina are these changes associated with a localised loss of retinal function. Preliminary data from images of the photoreceptor mosaic using CSLO suggests a strong correlation between co-localised cone counts and mfERG amplitude. These studies demonstrate a close association between changes in structure and function in myopia due to retinal stretching, but also suggest important underlying differences in myopic cell function. The structure- function relationship in RP is not always linear, but is dependent on retinal location and the precise nature of the measurements used. Empirical measures of cone density from retinal images could enhance evaluation of retinal structures in myopia and RP. Combining complementary measurements from ocular imaging and psychophysics with mfERG amplitude and timing demonstrates great potential for evaluating local retinal structure-function and function-function relationships in different eye conditions.

This thesis has investigated some of the cellular and sub-cellular mechanisms involved in three of the major blood flow autoregulation pathways of the retina, including pressure-autoregulation, regulation according to endothelium-derived factors. and neurovascular coupling. Myogenic responses represent the changes in vascular tone evoked by alterations in intra• luminal pressure, and they are mediated by vascular smooth muscle cell (VSMC) stretch and de polarisation. KCI evoked depolarisation of the VSMC of isolated retinal arterioles was used to investigate the changes to sub•cellular Ca2+ signaling underlying this pathway. Depolarisation triggers an increase in [Ca2+]i in VSMC mediated by voltage-sensitive L-type Ca2+ channels, and a subsequent stimulation of Ca2+ release from the sarcoplasmic reticulum via ryanodine sensitive (RyR) channels - which manifests as an increase in the frequency of spontaneous Ca2+ oscillations. The application of the endothelial-derived endothelin-l (Et-l) to isolated retinal arterioles caused elevations in both Ca2+ oscillations and sparks, as well as an increase in VSMC [Ca2+Ji. This reaction was mediated by an activation of EtAR on the VSMC plasma membrane and a stimulation of phospholipase C. This causes the production of inositol triphosphate (IP3). which activates Ca2+ release from the SR via IP3R. It was also found that RyR channels were also activated by Et-l, suggesting IP3R-RyR crosstalk. Retinal wholemount preparations were also employed to investigate the role of the neurotransmitter GABA in mediating vascular responses. The application of high concentrations of GABA evoked predominately vasodilation responses, mediated by GABAB receptors. It was also shown that GABA appears to make some contribution to baseline vascular tone, as the application of GABA receptor antagonists to un-constricted vessels evoked vasoconstrictions. Immunohistochemistry studies have indicated that GABAA and GABAB receptors are expressed on Muller cells, which have been linked to neurovascular coupling in the past suggesting a possible pathway for this vascular reaction.