Abstract
Purpose: :
Dendritic shrinkage in the lateral geniculate nucleus (LGN) has been identified as an early event in primate experimental glaucoma. We have previously shown dendritic loss and shrinkage in the superior colliculus (SC) in a rat glaucoma model. In the current study, we investigated dendritic changes in the LGN in the same rat model in order to further determine the effects of retinal neurodegeneration on central targets of retinal axons.
Methods: :
Ocular Hypertension (OHT) was induced in rats in the left eye using the Morrison method. Glaucoma animals and age matched controls were then sacrificed at 16 and 32 weeks (at least n=3 per group). Pseudo-sagittal fixed slices (400µm) from the contralateral brain section were prepared. Carbocyanine dye DiI (0.1%) was applied to the optic radiation to retrogradely label the neurons in the dorsal lateral geniculate nucleus (dLGN). The slices were incubated in PBS at 37°C for 7 days, following which confocal microscopy of neurons in dLGN was performed. The cells were classified into two types as relay neuron type 1 (LG1), relay neuron type 2 (LG2) (minimum 10 cells per type). The number of dendrites and mean dendritic length were measured using ImageJ software and statistical analysis using one way ANOVA was performed.
Results: :
We found both age related and glaucoma related changes in dendritic morphology. In the OHT group, the number of dendrites significantly decreased from 16 (LG1, 5±1; LG2, 3±0) to 32 (LG1, 3±0; LG2, 2±1) weeks (p<0.05), and the mean dendritic length also significantly reduced from 16 (LG1, 15±2µm; LG2, 12±1µm) to 32 (LG1, 10±2µm; LG2, 9±2µm) weeks (p<0.05). In the control group, the dendritic number significantly decreased from 16 (LG1, 7±1; LG2, 4±1) to 32 (LG1, 4±1; LG2, 3±0) weeks (p<0.05), and the mean dendritic length significantly reduced from (LG1, 23±4µm; LG2, 18±3µm) to 32 (LG1, 13±2µm; LG2, 12±1µm) weeks (p<0.05). Comparison between OHT and age-matched controls showed a significant decrease in both dendritic number and length (p<0.05).
Conclusions: :
Our results suggest that there is an age-related dendritic loss and shrinkage. Furthermore, in our OHT glaucoma model there is an additional reduction in dendritic number and length, and this may be indicative of secondary effects on the LGN following RGC degeneration.
Keywords: thalamus/lateral geniculate nucleus • aging • degenerations/dystrophies