Ovine eyes exhibit a robust steroid-induced ocular hypertensive response, with 100% occurrence in this trial. The mechanisms of steroid-induced glaucoma may be related to those involved in primary open-angle glaucoma and could provide insight into primary open-angle and clues to its treatment.

tion, mammalian lenses change shape from a rounder configuration (near focusing) to a flatter one (distance focusing). Thus the lens must have the capacity to change its volume, capsular surface area, or both. Because lens topology is similar to a torus, we developed an approach that allows volume determination from the lens cross-sectional area (CSA). The CSA was obtained from photographs taken perpendicularly to the lenticular anterior-posterior (A-P) axis and computed with software. We calculated the volume of isolated bovine lenses in conditions simulating accommodation by forcing shape changes with a custom-built stretching device in which the ciliary body-zonulae-lens complex (CB-Z-L) was placed. Two measurements were taken (CSA and center of mass) to calculate volume. Mechanically stretching the CB-Z-L increased the equatorial length and decreased the A-P length, CSA, and lens volume. The control parameters were restored when the lenses were stretched and relaxed in an aqueous physiological solution, but not when submerged in oil, a condition with which fluid leaves the lens and does not reenter. This suggests that changes in lens CSA previously observed in humans could have resulted from fluid movement out of the lens. Thus accommodation may involve changes not only in capsular surface but also in volume. Furthermore, we calculated theoretical volume changes during accommodation in models of human lenses using published structural parameters. In conclusion, we suggest that impediments to fluid flow between the aquaporin-rich lens fibers and the lens surface could contribute to the aging-related loss of accommodative power.lens volume calculation; intralenticular fluid movement; presbyopia; mammalian lens THE EYE IS ABLE TO FORM a clear image on the retina from objects situated within a wide range of distances due to a process called accommodation. In higher vertebrates, including humans, accommodation results from changes in crystalline lens shape and surface radii of curvature (13).When the ciliary muscle is relaxed and flattened against the sclera, the zonulae adjoining the ciliary body and the lens capsule are under tension and thus pulling eccentrically on the lens equator. This action causes the lens to adopt a relatively flattened shape with a larger equatorial diameter and a shorter A-P length, which allows focusing on virtual infinity (zero accommodation). When an individual focuses on a near object, the ciliary muscle contracts (shortening its distance to the lens equator), the zonulae relax, and the lens as a whole adopts a relatively rounded shape, which is its normal tendency. Physically, these changes in lens shape inevitably must involve changes in either capsular surface area or lens volume, or both.Classic theories of lenticular accommodation suggest that the volume of the intraocular crystalline lens remains constant during the accommodation process (16,17,30). No empirical studies have demonstrated that the volume actually stays constant. Because of the physical principle mentioned abov...

To determine whether the bovine eye develops elevation of intraocular pressure (IOP) in response to topical corticosteroid use and to develop a reliable model of steroid-induced elevation of IOP in an animal.Methods: Intraocular pressure was monitored by Perkins applanation tonometry in a group of 12 cows receiving topically administered prednisolone acetate in 1 eye 3 times a day for a period of 49 days after the establishment of baseline IOP values. Perkins readings were converted to IOP in mm Hg using calibration curves derived from in vitro cannulation manometric experiments and validated with in vivo manometric measurements. Intraocular pressure was also monitored for 50 days after the discontinuation of corticosteroid therapy.Results: Intraocular pressure began to increase after 3 weeks of treatment in 100% of the cow eyes receiving corticosteroid and reached a peak 1 week later. Peak interocular IOP differences between the corticosteroid-treated eye and the fellow control eye reached up to 15 mm Hg and began to decline after the discontinuation of treatment but remained significantly elevated for a period of 3 more weeks.Conclusions: Bovine eyes exhibit a robust steroidinduced ocular hypertensive response, with 100% occurrence in this trial. The IOP elevation caused by corticosteroid slowly subsides after discontinuation of treatment.Clinical Relevance: The mechanisms of steroidinduced glaucoma may be related to those involved in primary open-angle glaucoma and could provide the clues to elucidate the pathogenesis of the latter. The high prevalence of corticosteroid-induced elevation of IOP in the cow and the large amount of tissue available will permit studies on the mechanism of this phenomenon not previously possible.

A single dose of a gene therapy vector carrying an inducible metalloproteinase human gene can both protect against the IOP increase produced by corticosteroid instillation in the sheep model and quickly reverse the IOP increase previously elicited by the corticosteroid. These results are a first step toward a treatment of steroid-glaucoma with inducible overexpression of extracellular matrix modulator genes.

Steroid-induced IOP elevation alters gene expression in the bovine TM. Identification of genes with changing expression in this model of open-angle glaucoma may help elucidate the primary changes occurring at the molecular level in this condition.