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 (rd s) 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 h omozygous rds/rds retinas which lack photoreceptor outer segments and heter ozygous rds/+ retinas which have short malformed outer segments. Homozygous retinas exhibited depressed dopamine synthesis and utilization while the h eterozygous retina retained a considerable level of activity which was, nev ertheless, significantly lower than that of normal retinas. By one year, he terozygous rds/+ retinas which had lost half of the photoreceptors still ma intained significant levels of dopamine metabolism. Normal characteristics of dopamine metabolism such as a spike in dopamine utilization at light ons et were observed in mutant retinas. However, light intensity-dependent chan ges 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 c an 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 abnorma l patterns of dopamine utilization could be expected in such diseased retin as. (C) 2000 Elsevier Science B.V. All rights reserved.