Effect of general anesthetics on IOP in rats with experimental aqueous outflow obstruction.

PURPOSE: To determine the effect of several common general anesthetics on intraocular pressure (IOP) after experimental aqueous outflow obstruction in the rat. METHODS: A single episcleral vein injection of hypertonic saline was used to sclerose aqueous humor outflow pathways and produce elevated IOP in Brown Norway rats. Animals were housed in either standard lighting or a constant low-level light environment. Awake IOPs were determined using a TonoPen (Mentor, Norwell, MA) immediately before induction of anesthesia by either isoflurane, ketamine, or a mixture of injectable anesthetics (xylazine, ketamine, and acepromazine). For each anesthetic, IOPs were measured immediately after adequate sedation (time 0) and at 5-minute intervals, up to 20 minutes. RESULTS; Awake IOPs ranged from 18 to 52 mm Hg. All anesthetics resulted in a statistically significant (P: < 0.01) reduction in measured IOP at every duration of anesthesia when compared with the corresponding awake IOP. With increasing duration of anesthesia, measured IOP decreased approximately linearly for both the anesthetic mixture and isoflurane. However, with ketamine, IOP declined to 48% +/- 11% (standard lighting) and 60% +/- 7% (constant light) of awake levels at 5 minutes of anesthesia, where it remained stable. In fellow eyes, the SD of the mean IOP in animals under anesthesia was always greater than the corresponding SD of the awake mean. Anesthesia's effects in normal eyes and eyes with elevated IOP were indistinguishable. CONCLUSIONS: All anesthetics resulted in rapid and substantial decreases in IOP in all eyes and increased the interanimal variability in IOPs. Measurement of IOP in awake animals provides the most accurate documentation of pressure histories for rat glaucoma model studies.

Patterns of intraocular pressure elevation after aqueous humor outflow obstruction in rats.

PURPOSE: To determine the diural intraocular pressure (IOP) response of Brown Norway rat eyes after sclerosis of the aqueous humor outflow pathways and its relationship to optic nerve damage. METHODS: Hypertonic saline was injected into a single episcleral vein in 17 animals and awake IOP measured in both the light and dark phases of the circadian cycle for 34 days. Mean IOP for light and dark phases during the experimental period were compared with the respective pressures of the uninjected fellow eyes. Optic nerve cross sections from each nerve were graded for injury by five independent masked observers. RESULTS: For fellow eyes, mean light- and dark-phase IOP was 21 +/- 1 and 31 +/- 1 mm Hg, respectively. For four experimental eyes, mean IOPs for both phases were not altered. Six eyes demonstrated significant mean IOP elevations only during the dark phase. Of these, five showed persistent, large circadian oscillations, and four had partial optic nerve lesions. The remaining seven eyes experienced significant IOP elevations during both phases, and all had extensive optic nerve damage. CONCLUSIONS: Episcleral vein injection of hypertonic saline is more likely to increase IOP during the dark phase than the light. This is consistent with aqueous outflow obstruction superimposed on a circadian rhythm of aqueous humor production. Because these periodic IOP elevations produced optic nerve lesions, both light- and dark-phase IOP determinations are necessary for accurate correlation of IOP history to optic nerve damage in animals housed in a light- dark environment.

Microvasculature of the rat optic nerve head.

PURPOSE: To describe the arterial blood supply, capillary bed, and venous drainage of the rat optic nerve head. METHODS: Ocular microvascular castings from 6 Wistar rats were prepared by injection of epoxy resin through the common carotid arteries. After polymerization, tissues were digested with 6 M KOH, and the castings washed, dried, and coated for scanning electron microscopy. RESULTS: Immediately posterior to the globe, the ophthalmic artery trifurcates into the central retinal artery and two posterior ciliary arteries. The central retinal artery directly provides capillaries to the nerve fiber layer and only contributes to capillary beds in the neck of the nerve head. The remainder is supplied by branches of the posterior ciliary arteries that are analogous to the primate circle of Zinn-Haller. Arterioles arising from these branches supply the capillaries of the transitional, or laminar, region of the optic nerve head. These capillaries are continuous with those of the neck and retrobulbar optic nerve head. All optic nerve head capillaries drain into the central retinal vein and veins of the optic nerve sheath. A flat choroidal sinus communicates with the central retinal vein, the choriocapillaris, and with large veins of the optic nerve sheath. CONCLUSIONS: The microvasculature of the rat optic nerve head bears several similarities to that of the primate, with a centripetal blood supply from posterior ciliary arteries and drainage into the central retinal and optic nerve sheath veins. Association of nerve sheath veins with the choroid represents an important difference from the primate.

Glaucoma drops control intraocular pressure and protect optic nerves in a rat model of glaucoma.

PURPOSE: To determine whether chronic topical glaucoma therapy can control intraocular pressure (IOP) and protect nerve fibers in a rat model of pressure-induced optic nerve damage. METHODS: Sixteen adult Brown Norway rats were-administered unilateral episcleral vein injections of hypertonic saline to produce scarring of the aqueous humor outflow pathways. Twice daily applications of either artificial tears (n = 6), 0.5% betaxolol (n = 5), or 0.5% apraclonidine (n = 5) were delivered to both eyes, and awake pressures were monitored with a TonoPen XL tonometer for 17 days before the rats were killed. RESULTS: For animals administered artificial tears, the mean IOP of the experimental eyes was 39 +/- 2 mm Hg compared with 29 +/- 1 mm Hg for the control eyes. This difference was statistically significant (P < 0.001). Mean IOPs in the experimental eyes of animals administered betaxolol and apraclonidine were 29 +/- 7 and 29 +/- 4 mm Hg, respectively, whereas the mean IOP in the control eyes was 28 +/- 1 mm Hg for both groups. There was no statistically significant difference among these values. The mean IOP for the experimental eyes in the betaxolol and apraclonidine groups was lower than that in animals administered artificial tears (P = 0.003). Quantitative histologic analysis of optic nerve damage in experimental eyes showed that four of the six animals administered artificial tears had damage involving 100% of the neural area. This degree of damage appeared in only 3 of 10 animals administered glaucoma therapy. Optic nerve protection was closely correlated with IOP history because damage was limited to less than 10% of the cross-sectional area in all animals in which the maximal IOP was less than or equal to 39 mm Hg, more than 2 SD below the mean value for eyes administered artificial tears. CONCLUSIONS: Topical glaucoma therapy in this model can prevent IOP elevation and protect optic nerve fibers.