Abstract
Purpose::
Head-down position causes a substantial IOP increase in mice (Aihara et al., Curr Eye Res 2003). Our purpose is to characterize the effect of postural IOP changes on retinal ganglion cell function in the DBA/2J mouse model of glaucoma.
Methods::
Three groups of DBA/2J mice (3 month old, n=7; 5 month old, n=7, 10 month old, n=7) were studied. Mice were anesthetized with 0.6 ml/Kg of a mixture of Ketamine (42.8 mg/ml), Xylazine (8.5 mg/ml) and Acepromazine (1.4 mg/ml) delivered I.P. IOP and the Pattern Electroretinogram (PERG) were sequentially measured at 0°, 60° head-down position, and 0°. IOP was measured with a Tonolab® rebound tonometer (Wan-Heng Wang et al., IOVS 2005). The PERG was recorded in response to high-contrast (95%), large-field (50 x 56 deg) horizontal gratings (0.05 cycles/deg spatial frequency) alternating at 1 Hz. All procedures were performed in compliance with the ARVO statement for use of animals in ophthalmic and vision research.
Results::
On average, 60º head-down induced significant, reversible IOP increases in all age groups (3 months: 13.3±0.4 to 17.8±1.1 mm Hg; 5 months: 14.6±1.2 to 20.0±1.8 mm Hg; 10 months: 20.0±1.3 to 26.2±1.3 mm Hg). Head-down position induced reductions of PERG amplitude in older (glaucomatous) mice but not in young (pre-glaucomatous) mice (3 months: 10.8±1.3 to 10.8 ±0.9 µV; 5 months: 8.7±0.9 to 4.5±0.5 µV; 10 months: 4.5±0.5 to 1.467±0.2 µV). IOP and PERG changes were negatively correlated (P<0.001) in 10 month old mice.
Conclusions::
Head-down (60º) position induces reversible IOP changes in DBA/2J mice. The impact of IOP elevation on RGC function is age-dependent. The amount of PERG reduction is more pronounced in older mice, in which the severity of disease is more advanced (Libby et al., Vis Neurosci 2005). The combined evaluation of postural changes of IOP and PERG may represent a powerful, non invasive tool to evaluate IOP-dependent retinal ganglion cell vulnerability in mouse models of glaucoma.
Keywords: ganglion cells • genetics • degenerations/dystrophies