GENE THERAPY RESCUES S-CONE AT EARLY AGE IN A MOUSE MODEL OF LEBER CONGENITAL AMAUROSIS.

黎霞   庞继景   孔繁圣   戴旭峰   郑钦相   李文生   周翔天   吕帆   瞿佳

温州医学院眼视光学院   Ophthalmology University of Florida Gainesville FL U.S.A   325027

PURPOSE.To test whether AAV-mediated RPE65 expression could prevent earlier S-cone degeneration in rd12 mice，a naturally occurring animal model of human Leber congenital amaurosis with a recessively inherited RPE65 mutation.METHODS.At P14 and P35，one eye of 20 rd12 mice was subretinally injected with 1 microliter of scAAV5-smCBA-hRPE65.The contralateral eyes were not injected.One month after injection，the treated rd12 mice and the age matched normal C57BL/6J mice were examined by full-field photopic single-flash ERGs and ultraviolet-cone ERG，followed by the biochemical and morphological examinations.RESULTS.Almost all S-cones were maintained when injection was performed at P14.P14 treatment lead to almost normal cone specific PNA staining and normal S-cone opsin labeling，cone ERGs showed almost similar signals comparing with the C57BL/6J mice.Only minimal S-cones remained when injection was applied at P35.CONCLUSIONS.Our results suggest that only in time genetic intervention can prevent the very early S-cone degeneration in rd12 mice，thus supporting continuation of current LCA2 clinical trials with an added emphasis on cone subtype analysis and early intervention.