We allocated 110 DBA/2NNia mice of either sex to one of two feeding re
gimens: ad libitum (AL) or food restriction (FR) to 60% of the amount
consumed by the AL group. The mice were examined at 3, 6, 9, 12, 18, a
nd 24 months (at 3 months, only AL mice were examined). During the rem
aining periods approximately equal numbers (n = 10) of mice of both se
xes and diet groups were examined. Peripheral anterior synechia was th
e first glaucoma-associated lesion observed and was present in 8 of 10
AL female mice, 6 of 10 AL males, and 1 FR male at 6 months. At 9 mon
ths peripheral anterior synechia was present in all AL females and was
accompanied by depletion of retinal ganglion cells and degeneration o
f the optic nerves and optic tracts. Ninety percent of the eyes in the
AL males also had peripheral anterior synechia at 9 months, but gangl
ion cell depletion and optic nerve degeneration were not observed as f
requently. Neovascular membranes in the iridocorneal angle, a componen
t of peripheral anterior synechia, were first observed at 9 months in
approximately 55% of the globes of the AL mice and 5% of the FR mice.
This was a major difference in the microscopic features of synechia be
tween the diet groups and resulted in increased severity of synechia i
n the AL mice compared with their FR cohorts. Degeneration of the opti
c nerves and tracts was characterized by atrophy, astrogliosis, increa
se in cellularity, fragmentation of axons, and loss of myelin. Glaucom
a in the FR mice of both sexes was less severe than in their AL counte
rparts. The most severely affected were AL females, followed by FR fem
ales, AL males, and FR males. Food restriction reduced the incidence a
nd severity of the ocular lesions in females at all periods. The prima
ry benefit of FR in males occurred during the 6- and 9-month periods w
hen the incidence and severity of the glaucoma-related lesions were re
duced; in the succeeding months the major benefit was minimal reductio
n of the severity of the lesions.