Abstract
Purpose: :
DBA/2J (D2) mice spontaneously develop progressive IOP elevation and retinal ganglion cell (RGC) dysfunction that precedes RGC axon death (Saleh et al, IOVS 2007). We tested the hypothesis that head-up body posture lowers IOP, resulting in improvement of RGC dysfunction.
Methods: :
RGC function was evaluated in anesthetized (Ketamine/Xylazine) D2 mice (2 month old, n= 7, 6 month-old, n= 7, 10 month-old, n= 7) by means of the PERG (IOVS Feb 2007;48(2):745-51). IOP was measured with Tonolab rebound tonometer. IOP and PERG were measured with mice in horizontal position (baseline), during 60 deg head-up body posture (tilted), and again in horizontal position (recovery).
Results: :
In agreement with previous results (Saleh et al, IOVS 2007), IOP progressively increased and PERG amplitude progressively decreased with increasing age. In all age groups, head-up tilt consistently reduced IOP by ~ 5.5 mm Hg (2 month old: -5.28 ± 0.48 mm Hg; -32.2%; 6 month old: -5.57 ± 0.97 mm Hg, -26.42%; 10 month old: -6.14 ± 0.90 mm Hg, -21.7%) compared to horizontal (P<0.01). Head-up tilt did not induce PERG amplitude changes in 2 month-old mice. By contrast, the abnormal PERG amplitude of 6 month-old mice (-52.7 ± 18.6% compared to the mean amplitude of 2 month old) recovered ~22% (-31.01 ± 31.2% compared to 2 month old, P<0.05); the abnormal PERG amplitude of 10 month-old mice (-74.7 ± 8.8% compared to 2 month old) recovered ~26% (-48.651 ± 10.4% compared to 2 month old, P<0.01). Both IOP and PERG returned to baseline values in the recovery condition. The photopic flash-ERG was similar in all age group and did not change upon tilting.
Conclusions: :
Recoverable PERG amplitude with IOP lowering in 6 and 10 month old DBA/2J mice implies that age-related loss of RGC function is due to IOP-dependent, reduced responsiveness of viable retinal neurons rather than lack of activity of dead neurons. Head-up tilt represents a non-invasive way to probe the potential for recovery of RGC dysfunction in DBA/2J mice.
Keywords: ganglion cells • intraocular pressure • genetics