Carlos Gias

　　美国UCL 大学眼科研究所

　　Purpose:The aim of the current study was to determine the progress of neural functional degeneration in a rodent model of retinal dystrophy。

　　Method:Cortical responses were measured with optical imaging of intrinsic signals using gratings of various spatial frequencies and bright white stimulation in Royal College of Surgeons(RCS)rats of various ages along with appropriate non-dystrophic controls.Local field potentials(LFP)and multiunit activity(MUA)were also measured across cortical layers to study in detail the underlying electrical activity.In addition，an anatomical method was employed to study light-responsiveness(light induced nuclear cfos)in the retina specifically targeting retinal dopamine neurons.In order to visualise surviving photoreceptors，retinal wholemounts were co-labelled for either melanopsin or cone opsins。

　　Results:Cortical activity can be elicited in response to gratings of different spatial frequencies and light stimulation as measured with optical imaging and electrophysiology in the non-dystrophic rats from the age of 4 weeks.Light-induced nuclear cfos(of variable intensity)was found in the majority of dopaminergic cell nuclei in non-dystrophic rats.In the RCS rat，we found a substantial reduction in the cortical processing of gratings across a wide range of spatial frequencies and an increase in the latency of the cortical response as early as four weeks of age.Surviving cones were found in all retinal degenerate animals and following light exposure there was robust nuclear cfos staining in melanopsin cells regardless of age or retinal dystrophy.By 8 weeks of age，the light-induced cfos response was severely compromised in the RCS rat being almost absent by 3 months.However，at 16 months there was a significant re-activation in the cfos response to light exposure。

　　Conclusion:Given that the cortical processing of gratings has not fully developed at 4 weeks of age，the results presented here show that degeneration in the cortical response of the RCS rat start before development has been completed.Also，despite loss of neural function early in retinal dystrophy，we report here evidence of plasticity within the system leading to functional neural reactivation.