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A. A. Vugler, M. Semo, C. Gias, P. J. Coffey; Advancing Retinal Dystrophy Reveals Increased Potency of Melanopsin Signaling. Invest. Ophthalmol. Vis. Sci. 2010;51(13):678.
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Previous work indicates that melanopsin-driven intraretinal communication can activate a subpopulation of retinal dopamine neurons (Zhang et al., 2008). However, little is known about the spatial characteristics of this response and if the potency of melanopsin signalling changes temporally with advancing retinal degeneration.
We use light-driven cfos expression in tyrosine hydroxylase positive cells (TH-fos) to study the potency of intraretinal signalling at different stages of retinal dystrophy. Animal models studied include RCS rats and rd/rd cl mice, together with appropriate wildtype controls. As a separate measure, we employ a behavioural assay (photophobia) to assess melanopsin functionality with increasing age in rd/rd cl mice.
In wildtype animals, robust light-driven cfos activation was found in the majority of TH cells, which persisted throughout the course of the day. In RCS dystrophic rats, deficits in light-driven fos activation were obvious by 30 days of age in the central/ventral retina. This decline in TH cell activation continued until only minimal activation persisted dorsally at 14 weeks. In aged RCS dystrophics (16 months), there was a significant elevation in light driven TH-fos compared to that seen in younger animals. In rd/rd cl mice aged between 3-5 months, we could also detect a small population of light activated TH cells in central/dorsal retina. A comparison between numbers of TH-fos cells in young versus old (14 month) rd/rd cl mice revealed a significant increase with age. An increased responsiveness to light in aged rd/rd cl mice was also observed at the behavioural level, with older animals showing a decreased latency in their photophobic response.
Here we identify an anatomically defined population of TH cells that respond to light in an animal lacking rods and cones. The strength of this intra-retinal signalling increases with age, as does the light-responsiveness of these animals at the behavioural level. Our data suggest that an increase in the potency of melanopsin-driven signalling may be a characteristic feature of advanced retinal degenerations.
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