Holcombe D J, Lengefeld N, Gole G A, Barnett N L
School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia.
Br J Ophthalmol. 2008 May;92(5):683-8. doi: 10.1136/bjo.2007.133223. Epub 2008 Feb 22.
BACKGROUND/AIMS: To correlate ganglion cell function with defined parameters of the elevated intraocular pressure profile (IOP) in a mouse glaucoma model and to determine the temporal relationship of these functional changes with ganglion cell death.
Unilateral chronic ocular hypertension was induced in C57BL6/J mice by laser ablation of the limbal episcleral veins. Scotopic flash electroretinograms were recorded after 5, 10, 20, and 40 days to isolate specific outer and inner retinal responses. Inner retinal function was correlated with the pressure differential between treated and non-treated eyes at the time of electroretinographic recording, and with the cumulative IOP insult (the integral of the IOP.time profile). Peripheral and central ganglion cell densities were quantified by Brn-3 immunohistochemistry.
Elevated IOP induced a preferential deficit in inner retinal function. The positive scotopic threshold response (pSTR) was suppressed by 68% on day 5, by 50% on day 10, by 54% on day 20 and by 46% on day 40 after laser treatment. Inhibition of the STR correlated with the pressure differential between treated and non-treated eyes but not with the IOP.time integral. Inner retinal dysfunction preceded the progressive death of ganglion cells. Ganglion cell loss occurred preferentially in peripheral retina and correlated with the cumulative IOP insult.
We have demonstrated specific inner retinal dysfunction in an inducible mouse glaucoma model. STRs are sensitive to elevated IOP per se, and their early suppression reflects ganglion cell dysfunction rather than cell death. The correlation between IOP elevation and suppression of inner retinal function, in the context of the temporal progression of ganglion cell death, suggests that a portion of the IOP-mediated ganglion cell dysfunction may be reversible.
背景/目的：在小鼠青光眼模型中，将神经节细胞功能与眼内压升高曲线（IOP）的特定参数相关联，并确定这些功能变化与神经节细胞死亡的时间关系。
通过激光烧灼角膜缘巩膜静脉，在C57BL6/J小鼠中诱导单侧慢性高眼压。在第5、10、20和40天记录暗视闪光视网膜电图，以分离特定的视网膜外层和内层反应。视网膜内层功能与视网膜电图记录时治疗眼和未治疗眼之间的压差以及累积IOP损伤（IOP-时间曲线的积分）相关。通过Brn-3免疫组织化学定量外周和中央神经节细胞密度。
眼压升高导致视网膜内层功能出现优先缺陷。激光治疗后第5天，阳性暗视阈值反应（pSTR）被抑制68%，第10天被抑制50%，第20天被抑制54%，第40天被抑制46%。STR的抑制与治疗眼和未治疗眼之间的压差相关，但与IOP-时间积分无关。视网膜内层功能障碍先于神经节细胞的渐进性死亡。神经节细胞丢失优先发生在外周视网膜，且与累积IOP损伤相关。
我们在可诱导的小鼠青光眼模型中证明了特定的视网膜内层功能障碍。STR本身对眼压升高敏感，其早期抑制反映了神经节细胞功能障碍而非细胞死亡。在神经节细胞死亡的时间进程中，眼压升高与视网膜内层功能抑制之间的相关性表明，部分眼压介导的神经节细胞功能障碍可能是可逆的。
