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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.

Ocular Pressure-Volume Relationship and Ganglion Cell Death in Glaucoma