The purpose of this experiment was to test the susceptibility to retinal ganglion cell (RGC) axon loss and RGC layer cell loss from experimental glaucoma among 3 mouse strains, and between younger and older mice. We obstructed the mouse aqueous outflow channels by injecting 2 μL of 6 μm diameter, polystyrene beads followed by 3 μL of viscoelastic solution into the anterior chamber with a glass micropipette. We evaluated intraocular pressure (IOP) and damage to RGC as measured by optic nerve axon counts and RGC layer neuron counts in 3 strains of young mice (2 month old C57BL/ 6, DBA/2J, and CD1) and 10 month C57BL/6 mice. Bead and viscoelastic injection produced IOP elevation at ≥1 time point in 94.1% of eyes (112/119), with mean IOP difference from fellow eyes of 4.4 ± 3.0 mmHg. By 6-12 weeks, injected eyes were 10.8% longer and 7.6% wider (p <0.0001). Young DBA/2J and C57BL/6 eyes increased axial length significantly more than young CD1 or older C57BL/6 (all p ≤0.02). RGC layer and axon loss was greatest in CD1 mice, significantly more than the other groups (p from 0.04 to <0.0001). Young C57BL/6 eyes elongated more and lost more RGC layer cells than older C57BL/6 mice (p =0.02 and 0.01, respectively). With this mouse glaucoma model, there was differential susceptibility to ocular elongation and RGC layer and axon damage among mouse strains and by age. Factors that determine sensitivity to RGC injury can be studied using transgenic mouse strains with inducible models.

Purpose To assess the neuroprotective effect of virally-mediated over-expression of ciliary derived neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in experimental rat glaucoma. Methods Laser-induced glaucoma was produced in one eye of 224 Wistar rats after injection of adeno-associated viral vectors (type 2) containing either CNTF, BDNF or both, using saline injected eyes and uninjected glaucoma eyes as controls. IOP was measured with the TonoLab and semi-automated optic nerve axon counts were performed by masked observers. IOP exposure over time was adjusted in multivariate regression analysis to calculate the effect of CNTF and BDNF. Results By multivariate regression, CNTF had a significant protective effect, with 15% less RGC axon death (p < 0.01). Both combined CNTF—BDNF and BDNF over-expression alone had no statistically significant improvement in RGC axon survival. By Western blot, there was a quantitative increase in CNTF and BDNF expression in retinas exposed to single viral vectors carrying each gene, but no increase with sequential injection of both vectors. Conclusion These data confirm that CNTF can exert a protective effect in experimental glaucoma. The reason for a lack of observed effect with the BDNF overexpression groups is unclear, but may be a function of the level of neurotrophin expression achieved.

After nerve crush, RGCs and axons died rapidly, and dendritic structure decreased moderately in remaining RGCs. Glaucoma caused an increase in RGC dendrite structure and soma size at 3 weeks.