Purpose:
Dendritic pruning has been suggested as an early sign in neurodegeneration (1,2). However, its development in glaucoma has not been well established. We have previously demonstrated dendritic shrinkage and loss in the superior colliculus (SC) and lateral geniculate nucleus (LGN) in a rat model of experimental glaucoma. In this study, we investigated dendritic changes in the RGCs in the same model.
Methods:
Ocular Hypertension (OHT) was induced in rats aged 6-8 weeks in the left eye only using the Morrison method. The right eyes were used as controls (CTL). The animals (at least n=3/group) were sacrificed at 4, 8, 16 and 32 weeks, following which enucleated eyes were carefully dissected. Carbocyanine dye DiI was used to label RGCs by biolistic staining of fresh retinae. Confocal microscopy of RGCs was performed. On analysis, RGCs were classified according to Perry (3) (RGC (R) type I, II and III) (total of 240 cells, 30 cells per group)). Dendritic length and number of dendrites were measured using ImageJ software and statistical analysis using one way ANOVA was performed as previously described.
Results:
We found both age related and glaucoma related changes in dendritic morphology. In the CTL group, the mean dendritic length significantly decreased over time from 4 to 32 weeks for RI and RII (P<0.05). In the OHT group, there was significant dendritic shrinkage from 4 to 32 weeks for RI and RIII (P<0.05). Furthermore a trend of dendritic loss was demonstrated. There was a significant increase in dendritic shrinkage in OHT eyes compared to controls from 4 to 32 weeks for RIII (P<0.05).
Conclusions:
Our results suggest that there is an age-related dendritic shrinkage and loss. Furthermore, in OHT eyes we found a significant reduction early (at 4 weeks) after intraocular pressure (IOP) surgery. This indicates that RGC dendritic pruning is an early event in experimental glaucoma.Acknowledgement:Professor David Becker, Visufarma and Medical Research.
References:
1 Weber AJ et al. (1998) Invest Ophthalmol Vis Sci 39:2304-2320.2 Jakobs TC et al. (2005) J Cell Biol 171:313-325.3 Perry VH. (1979) Proc R Soc Lond B Biol Sci. 204(1156):363-375.Council.
Keywords: ganglion cells • retina • degenerations/dystrophies