Diurnal metabolism of dopamine in dystrophic retinas of homozygous and heterozygous retinal degeneration slow (rds) mice.
Dopamine metabolism was studied in dystrophic retinal degeneration slow (rds) mice which carry a mutation in the rds/peripherin gene. RDS mutations in humans cause several forms of retinal degeneration. Dopamine synthesis and utilization were analyzed at various time points in the diurnal cycle in homozygous rds/rds retinas which lack photoreceptor outer segments and heterozygous rds/+ retinas which have short malformed outer segments. Homozygous retinas exhibited depressed dopamine synthesis and utilization while the heterozygous retina retained a considerable level of activity which was, nevertheless, significantly lower than that of normal retinas. By one year, heterozygous rds/+ retinas which had lost half of the photoreceptors still maintained significant levels of dopamine metabolism. Normal characteristics of dopamine metabolism such as a spike in dopamine utilization at light onset were observed in mutant retinas. However, light intensity-dependent changes in dopamine utilization were observed in normal but not rds/+ retinas. The findings of this study suggest that human patients with peripherin/rds mutations, or other mutations that result in abnormal outer segments that can still capture light, might maintain light-evoked dopamine metabolism and dopamine-dependent retinal functions during the progression of the disease, proportional to remaining levels of light capture capabilities. However, visual deficits due to reduced light-evoked dopamine metabolism and abnormal patterns of dopamine utilization could be expected in such diseased retinas.
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Department of Pharmacology, University of Texas Health Science Center, San Antonio, TX, USA. nir@uthscsa.edu
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics*; D064531:Peripherins; D010641:Phenotype; D010775:Photic Stimulation; D010786:Photoreceptor Cells / Q000473:pathology / Q000648:ultrastructure; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D004791:Enzyme Inhibitors; D006834:Hydrazines; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D064531:Peripherins; C578996:Prph2 protein, mouse; D015102:3,4-Dihydroxyphenylacetic Acid; C004297:3-hydroxybenzylhydrazine; D004298:Dopamine