We studied how GC death in glaucoma related to the intraocular pressure (IOP), eyeball volume (VS) and elasticity (volumetric KS and tensile ES), 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: VS (p = 0.0003), age (p = 0.0026) and IOP (but p = 0.0966). As indicated by average values, adult D2 mice (³6 months) suffered significant GC loss, low KS and ES, and universal expansion of VS with normal IOP. KS and ES 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 ΔVS » ΔVW, ΔVW-the change in the aqueous humor amount), we deduced equations on the ocular volume-pressure relationship: ΔIOP = KS*ΔVW/VS or ΔIOP = (2/3)*[1/(1-n)]*(H/R)*ES*ΔVW/VS (n, 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 KS and ES, expanded VS, and large ΔVW, 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.