IOP-Dependent Retinal Ganglion Cell Dysfunction in Glaucomatous DBA/2J Mice

Abstract

PURPOSE: To characterize the effect of postural IOP elevation and pharmacological IOP lowering on retinal ganglion cell (RGC) function in the DBA/2J mouse model of glaucoma. METHODS: Four groups of DBA/2J mice (3 months old, n = 7; 5 months old, n = 7; 10 months old, n = 7; and 11 months old, n = 8) were anesthetized by intraperitoneal injection (0.6 mL/kg) of a mixture of ketamine (42.8 mg/mL), xylazine (8.5 mg/mL), and acepromazine (1.4 mg/mL). IOP and pattern electroretinogram (PERG) were sequentially measured with mice at 0 degrees (horizontal), 60 degrees head-down, and again at 0 degrees . IOP and PERG were also measured before and after intraperitoneal mannitol 25% (2.5 g/kg) administration with mice in a horizontal position. RESULTS: The head-down position induced reversible IOP elevations of 32% to 38% in all age groups (P < 0.01), and age-dependent reductions of PERG amplitude (3 months: +3%; 5 months: -47%, P < 0.01; and 10 months: -65%, P < 0.01). Administration of mannitol to 11-month-old mice resulted in a reduction in IOP of approximately 38% (P < 0.01) and a PERG amplitude improvement of approximately 83% (P < 0.001). IOP and PERG amplitude changes were inversely correlated (10 months head-down r(2) = 0.58, P < 0.001; 10-month-old mannitol r(2) = 0.41, P < 0.001). For all conditions, the light-adapted flash ERG was unaltered. CONCLUSIONS: In the DBA/2J mouse, RGC susceptibility to artificial IOP elevation increases with age. Abnormal RGC function in older mice may be improved with IOP lowering. Evaluation of PERG changes in response to artificial IOP modulation may represent a powerful tool to assess noninvasively RGCs' susceptibility to IOP insult in genetically distinct mouse models of glaucoma.