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T.-H. Chou, W. Lee, I. Nose, J.-M. Parel, V. Porciatti; Susceptibility of Retinal Ganglion Cell Function to Acute IOP Modulation in DBA/2J Glaucoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5484.
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© ARVO (1962-2015); The Authors (2016-present)
Mechanisms linking IOP with retinal ganglion cell (RGC) damage in glaucoma are little understood. Changes in RGC function associated with induced IOP modulation may provide an index of RGC susceptibility to IOP stress. Acute IOP modulation can be obtained in DBA/2J (D2) mice of any age by changes of body posture: head-down (HD) causes IOP rise, and head-up (HU) causes IOP fall [IOVS 2007, 48: 4573-9; IOVS 2008, 49: E-Abstract 1047]. We assessed the susceptibility of RGC function by measuring the changes in pattern electroretinogram (PERG) amplitude associated with HD-HU body posture, and also how posture-dependent PERG changes are influenced by IOP-lowering treatment.
D2 mice aged 6 months (n=6) and 2 months (n=5) were anesthetized with ketamine-xylazine. IOP (Tonolab) and PERG amplitude were sequentially (10-15 minutes apart) measured in 5 conditions: horizontal (H1); 60 deg head-down (HD); horizontal (H2); 60 deg head-up (HU); horizontal (H3). PERG amplitude differences between HU and HD conditions were considered as posture-dependent changes [PDC=(HU-HD)/mean(H1,H2)]. The experiment was repeated in 6 month-old D2 after treatment with Timolol maleate.
Baseline IOP was similar in 2 month old and 6 month old mice (20.6±1.6 and 21.3 ±4.6 mm Hg, respectively) and decreased after treatment in 6 mo mice (13.6 ± 2.6 mm Hg). Body tilt induced comparable IOP changes in 2 month old, 6 month old, and 6 month old-treated D2 mice. Mean IOP changes (HD-HU ± SD, mm Hg) were: 2mo: 10.3±2.9; 6mo: 7.8±1.3; 6mo-treated: 8.2±4.1. Body tilt induced PERG changes in 6 month-old D2 (PDC=0.51 ± 0.16, 95% C.I. 0.64-0.37). In 6 month-old D2 treated with timolol, as well as in 2 month-old D2, PDC were smaller and not significantly different from zero. In all groups of mice, IOP and PERG recovered baseline values after horizontal repositioning [H3 ≈ mean(H1,H2)].
The PERG signal is susceptible to HD/HU body tilt in D2 mice 6 month old but not in D2 mice 2 month old. Posture-dependent susceptibility of PERG signal in 6 month old D2 is abolished after treatment with Timolol maleate, which substantially reduces baseline IOP but spares posture-dependent IOP modulation. The protective effect of IOP-lowering therapy on age-related RGC loss in D2 mice [IOVS 2006, 47: 2498-507; Vision Res. 2002, 42: 2333-7] might be explained on the basis of reduced RGC susceptibility to IOP insult. The HD/HU approach might provide a means to predict long-term benefits of IOP-lowering or other neuroprotective treatments based on acute modifiability of PERG signal.
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