Nagaraju Mahesh, Saleh Maher, Porciatti Vittorio
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4573-9. doi: 10.1167/iovs.07-0582.
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.
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.
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.
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.
在DBA/2J青光眼小鼠模型中，研究姿势性眼压升高和药物性眼压降低对视网膜神经节细胞（RGC）功能的影响。
四组DBA/2J小鼠（3月龄，n = 7；5月龄，n = 7；10月龄，n = 7；11月龄，n = 8）通过腹腔注射（0.6 mL/kg）氯胺酮（42.8 mg/mL）、赛拉嗪（8.5 mg/mL）和乙酰丙嗪（1.4 mg/mL）的混合物进行麻醉。依次在小鼠处于0度（水平）、头向下60度以及再次回到0度时测量眼压和图形视网膜电图（PERG）。还在水平位的小鼠腹腔注射25%甘露醇（2.5 g/kg）前后测量眼压和PERG。
头向下姿势在所有年龄组中均引起眼压可逆性升高32%至38%（P < 0.01），以及PERG振幅随年龄降低（3个月：+3%；5个月：-47%，P < 0.01；10个月：-65%，P < 0.01）。对11月龄小鼠给予甘露醇导致眼压降低约38%（P < 0.01），PERG振幅改善约83%（P < 0.001）。眼压和PERG振幅变化呈负相关（10个月头向下r(2) = 0.58，P < 0.001；10月龄甘露醇r(2) = 0.41，P < 0.001）。在所有条件下，明适应闪光视网膜电图均未改变。
在DBA/2J小鼠中，RGC对人工眼压升高的易感性随年龄增加。老年小鼠中异常的RGC功能可通过降低眼压得到改善。评估PERG对人工眼压调节的反应变化可能是一种强大的工具，用于在基因不同的青光眼小鼠模型中无创评估RGC对眼压损伤的易感性。
