title: Constant illumination causes spatially discrete dopamine depletion in the normal and degenerate retina.
abstract: A fully competent retinal dopamine system underpins normal visual function. Although this system is known to be compromised both prior to and during retinal degeneration, the spatial dynamics of dopamine turnover within the degenerate retina are at present unknown. Here, using immunohistochemistry for dopamine in combination with quantitative optical density measurements, we reveal a global decline in retinal dopamine levels in the light adapted RCS dystrophic rat, which is restricted to plexiform layers in the dark. Pharmacological blockade of dopamine production with the drug alpha-methyl-p-tyrosine (AMPT) allows the direct visualisation of dopamine depletion in normal and degenerate retina in response to constant illumination. In normal retinae this effect is spatially discrete, being undetectable in perikarya and specific to amacrine cell fibres in sublamina 1 of the inner plexiform layer. A similar response was observed in the retinae of dystrophic rats but with a reduction in amplitude of approximately 50%. It is suggested that the pattern of dopamine depletion observed in rat retina may reflect an AMPT-resistant pool of perikaryal dopamine and/or a reduction in extrasynaptic release of this neurotransmitter in response to illumination in vivo. We conclude that the visualisation of dopamine depletion reported here represents a release of this neurotransmitter in the response to light. Turnover of dopamine in the dystrophic retina is discussed in the context of surviving photoreceptors, including the intrinsically photosensitive melanopsin ganglion cells of the inner retina.
authors.affiliation: Division of Cellular Therapy, Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK. a.vugler@ucl.ac.uk
authors.forename: A A
authors.initials: AA
authors.lastname: Vugler
authors.forename: P
authors.initials: P
authors.lastname: Redgrave
authors.forename: N J
authors.initials: NJ
authors.lastname: Hewson-Stoate
authors.forename: J
authors.initials: J
authors.lastname: Greenwood
authors.forename: P J
authors.initials: PJ
authors.lastname: Coffey
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D008027:Light; D008297:Male; D010786:Photoreceptor Cells / Q000502:physiology; D051381:Rats; D011922:Rats, Mutant Strains; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D012162:Retinal Degeneration / Q000473:pathology / Q000503:physiopathology*; D017299:Rod Opsins / Q000378:metabolism; D019805:alpha-Methyltyrosine / Q000494:pharmacology; D000099210:Melanopsin
chemical_list: D004298:Dopamine; D017299:Rod Opsins; D019805:alpha-Methyltyrosine; D000099210:Melanopsin