Pang Ji-Jie, Wu Samuel M
Department of Ophthalmology, Baylor College of Medicine, One Baylor Plaza, NC 205, Houston, Texas.
OBM Neurobiol. 2021;5(2). doi: 10.21926/obm.neurobiol.2102098. Epub 2021 May 20.
We studied how GC death in glaucoma related to the intraocular pressure (IOP), eyeball volume (V) and elasticity (volumetric K and tensile E), and eyeball volume-pressure relation. Glaucomatous GC loss was studied in DBA/2J (D2) mice with wild-type mice as controls. GCs were retrogradely identified and observed with a confocal microscope. The elasticity calculation was also done on published data from patients treated by a gas bubble injection in the vitreous cavity. The GC population in D2 mice (1.5- to 14-month-old) was negatively correlated with following factors: V (p = 0.0003), age (p = 0.0026) and IOP (but p = 0.0966). As indicated by average values, adult D2 mice (≥6 months) suffered significant GC loss, low K and E, and universal expansion of V with normal IOP. K and E in the patients were also lower upon prolonged eyeball expansion compared to acute expansion. Based on the results and presumptions of a closed and continuous eyeball space (thereby ΔV ≈ ΔV, ΔV-the change in the aqueous humor amount), we deduced equations on the ocular volume-pressure relationship: ΔIOP = KΔV/V or ΔIOP = (2/3)[1/(1-ν)]*(H/R)EΔV/V (ν, Poisson's ratio taken as 0.5; R, the curvature radius; and H, the shell thickness). Under normal atmospheric pressure, IOP of 1050 mmHg contributed only 1.26.6% of the pressure opposing the retina and eyeball shell. We conclude: 1) A disturbance of ocular volume-pressure homeostasis, mediated primarily by low K and E, expanded V, and large ΔV, is correlated with GC death in glaucoma and 2) D2 mice with GC loss and normal IOP may serve as animal models for human normal-tension glaucoma.
我们研究了青光眼患者视网膜神经节细胞（GC）死亡与眼压（IOP）、眼球体积（V）和弹性（体积弹性模量K和拉伸弹性模量E）以及眼球体积-压力关系之间的联系。以野生型小鼠作为对照，对DBA/2J（D2）小鼠的青光眼性GC丢失情况展开研究。利用共聚焦显微镜对GC进行逆行鉴定与观察。同时，依据玻璃体内注射气泡治疗患者的已发表数据进行弹性计算。D2小鼠（1.5至14月龄）的GC数量与以下因素呈负相关：V（p = 0.0003）、年龄（p = 0.0026）以及IOP（但p = 0.0966）。平均值表明，成年D2小鼠（≥6月龄）出现显著的GC丢失、低K和E，并且在眼压正常的情况下V普遍增大。与急性眼球扩张相比，长时间眼球扩张的患者其K和E也更低。基于封闭且连续的眼球空间的结果与假设（因此ΔV≈ΔV，ΔV为房水量的变化），我们推导了眼内体积-压力关系的方程：ΔIOP = KΔV/V或ΔIOP = (2/3)[1/(1 - ν)]*(H/R)EΔV/V（ν，泊松比取0.5；R，曲率半径；H，壳厚度）。在正常大气压下，10至50 mmHg的眼压仅占对抗视网膜和眼球壁压力的1.2%至6.6%。我们得出结论：1）主要由低K和E、增大的V以及大的ΔV介导的眼内体积-压力稳态紊乱与青光眼患者的GC死亡相关；2）GC丢失且眼压正常的D2小鼠可作为人类正常眼压性青光眼的动物模型。
