Dendritic pruning of retinal ganglion cells in a mouse model of dominant optic atrophy (ADOA)

Abstract

Abstract Purpose The model of ADOA (B6;C3‐Opa1Q285STOP ), displays visual dysfunction and optic nerve changes after 12 months age. We explore dendritic morphology of ON‐Centre and OFF‐Centre retinal ganglion cells (RGCs) in the mutant mouse. Methods Retinas of Opa1+/‐ mice (n=12) and age/sex matched Opa1+/+ (n=5), were flat‐mounted and RGCs labelled by Diolistics (DiI). Animals were assessed at <10 months of age (+/+ n=2, +/‐ n=2), 10‐15 months (+/+ n=1, +/‐ n=3) and 20> months (+/+ n=2, +/‐ n=7)). Retinas were fixed (4%PFA) and imaged (x20). Dendritic morphologies were analysed in image stacks of RGCs (ImageJ) and quantified by Sholl analyses (Matlab). Results Dendritic trees show decreased average dendritic field area at 10‐15 months (‐35.1%; p < 0.05; number of cells=12) and 20> months (‐48.3%; p < 0.0001; n=45). There is a decrease in the average total dendritic length in 10‐15 month mice (‐44.9%; p < 0.05; n=12) and 20> month mice (‐62.9%; p < 0.0001, n=45). Sholl analysis showed a marked difference in the dendritic arborisation of the 10‐15 month and the 20> month group. (SE were all non‐overlapping). There was no change in <10 month mice compared to controls (p > 0.05). There was no marked difference in dendritic density, implying pruning of secondary and tertiary dendrites, rather than primary dendrites. There was no statistical difference in average dendritic field area and average total dendritic length between Opa1+/‐ and Opa1+/+ in OFF‐centre cells in mice (at<10 months and 20> months). Conclusion The presence of dendritic pruning in the ON‐Centre RGCs of the OPA1+/‐ mouse model of ADOA offers a putative mechanism for the visual dysfunction observed. The changes precede onset of clinical visual loss, structural c