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M. Liu, A. Georgiou, L. Guo, T. E. Salt, M. F. Cordeiro; Dendritic Pathology in the Superior Colliculus in a Rat Model of Experimental Glaucoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5199.
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© ARVO (1962-2015); The Authors (2016-present)
Dendritic shrinkage in the lateral geniculate nucleus has been identified as an early event in primate experimental glaucoma. In rodents, the superior colliculus (SC) is the major site of termination of retinal axons. In this study, we investigated dendritic pathology in the SC in an experimental glaucoma rat model in order to determine whether retinal degeneration has an effect on central targets of retinal axons.
Ocular Hypertension (OHT) was induced in rats in the left eye only using the Morrison method. All animals had DARC imaging performed at regular intervals after IOP elevation. Glaucoma animals and age matched controls were then sacrificed at 4, 16 and 32 weeks (n=30, at least 3 per group). Carbocyanine dye DiI (0.1%) was applied to the SC in 400µm fixed brain slices using a glass micropipettete, and incubated in PBS at 37°C for seven days, following which confocal microscopy of neurons in the superficial SC was performed. The number of dendrites and mean dendritic length were measured using ImageJ software and statistical analysis using a two-tailed Student’s t-test was performed.
DARC imaging confirmed peak OHT RGC apoptosis occurred at 3 weeks. We found both glaucoma-related and age-related changes in dendritic morphology. In the OHT group, the number of dendrites (Dcount) and mean dendritic length (Dmean) significantly decreased from 4 (Dcount:7±2; Dmean:43±15µm) to 16 (Dcount:6±5; Dmean:41±16µm) weeks (p<0.05) and 16 to 32 (Dcount:3±1;Dmean:19±9µm) weeks (p<0.05), with linear regression analysis showing a significant reduction in all parameters over time (r2= 0.944 (Dcount) and 0.870 (Dmean)). In the control group, the Dcount and Dmean also significantly decreased from 16 (Dcount:7±3; Dmean:50±22µm) to 32 (Dcount:3±1; Dmean:32±9µm) weeks (p<0.05). Comparison between OHT and age-matched controls showed a reduction in Dmean, but this only reached statistical significance at 32 weeks (p<0.05). No differences were found with respect to Dcount.
Our results suggest that chronic ocular hypertension in this rat model significantly affects superior colliculus dendritic morphology over time, with a reduction in both the dendritic count and length. However, we were only able to demonstrate significant differences in dendritic shrinkage between experimental glaucoma and age-matched controls at 32 weeks, and this may be indicative of secondary effects on the SC following RGC apoptosis. Further work is needed in this area, but we have shown that SC dendritic pathology is IOP and age-related in the rat.
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