Glaucoma in food-restricted and ad libitum-fed DBA/2NNia mice.

We allocated 110 DBA/2NNia mice of either sex to one of two feeding regimens: 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, and 24 months (at 3 months, only AL mice were examined). During the remaining periods approximately equal numbers (n = 10) of mice of both sexes and diet groups were examined. Peripheral anterior synechia was the 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 months peripheral anterior synechia was present in all AL females and was accompanied by depletion of retinal ganglion cells and degeneration of the optic nerves and optic tracts. Ninety percent of the eyes in the AL males also had peripheral anterior synechia at 9 months, but ganglion cell depletion and optic nerve degeneration were not observed as frequently. Neovascular membranes in the iridocorneal angle, a component 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 between the diet groups and resulted in increased severity of synechia in the AL mice compared with their FR cohorts. Degeneration of the optic nerves and tracts was characterized by atrophy, astrogliosis, increase in cellularity, fragmentation of axons, and loss of myelin. Glaucoma in the FR mice of both sexes was less severe than in their AL counterparts. The most severely affected were AL females, followed by FR females, AL males, and FR males. Food restriction reduced the incidence and severity of the ocular lesions in females at all periods. The primary benefit of FR in males occurred during the 6- and 9-month periods when the incidence and severity of the glaucoma-related lesions were reduced; in the succeeding months the major benefit was minimal reduction of the severity of the lesions.