Ocular Pressure-Volume Relationship and Ganglion Cell Death in Glaucoma

We studied how GC death in glaucoma related to the intraocular pressure (IOP), eyeball volume (V(S)) and elasticity (volumetric K(S) and tensile E(S)), 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(S) (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(S) and E(S), and universal expansion of V(S) with normal IOP. K(S) and E(S) 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(S) ≈ ΔV(W), ΔV(W)-the change in the aqueous humor amount), we deduced equations on the ocular volume-pressure relationship: ΔIOP = K(S)*ΔV(W)/V(S) or ΔIOP = (2/3)*[1/(1-ν)]*(H/R)*E(S)*ΔV(W)/V(S) (ν, Poisson’s ratio taken as 0.5; R, the curvature radius; and H, the shell thickness). Under normal atmospheric pressure, IOP of 10~50 mmHg contributed only 1.2~6.6% of the pressure opposing the retina and eyeball shell. We conclude: 1) A disturbance of ocular volume-pressure homeostasis, mediated primarily by low K(S) and E(S), expanded V(S), and large ΔV(W), 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.