City Research Online

Abstract

The aim of this study was to determine the underlying cellular mechanism by which ethanol alters the standing potential of the human eye (the ethanol electro-oculogram). Using chamber experiments using animal explants of retinal pigment epithelium and retina, as well as cultured retinal pigment epithelial cells grown on filter inserts, were conducted to determine whether the retinal pigment epithelium was the target for ethanol. The human retinal pigment epithelial cell line, ARPE-19 was used to investigate changes in intracellular calcium concentration in response to ethanol. Human studies involving patients with cystic fibrosis were performed to determine the likely ionic channel involved in the ethanol-electro-oculogram.

Results indicated that ethanol was capable of elevating intracellular calcium concentration but that the source was from the extracellular pools. The likely ionic channel responsible for the light evoked electro-oculogram is the L-type calcium channel and this channel could be the route through which ethanol mediates the calcium-signal based on this finding. The amplitude of the ethanol evoked electro-oculogram was not dependent upon one functional chloride channel affected in cystic fibrosis and regulated by cyclic adenosine monophosphate dependent protein kinase A. This finding supports the role of a calcium-gated basolateral chloride channel being responsible for the ethanol-electro-oculogram. The fast oscillations in the cystic fibrosis subjects also showed higher or normal responses which are supportive of a recent finding in an animal model of this condition.

The findings of this study indicate that the ethanol-electro-oculogram is dependent upon calcium signalling. The earlier clinical studies have also shown that the ethanol-electro-oculogram is affected more than the light electro-oculogram in early retinal degenerations. Therefore, the results presented would suggest that calcium signalling is impaired in early retinal degenerations.

Publication Type:	Thesis (Doctoral)
Subjects:	R Medicine > RZ Other systems of medicine
Departments:	School of Health & Psychological Sciences > Optometry & Visual Sciences School of Health & Psychological Sciences > School of Health & Psychological Sciences Doctoral Theses Doctoral Theses

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