Topical retinoic acid in the treatment of experimental xerophthalmia in the rabbit.

The purpose of this study was to evaluate the efficacy of topical retinoic acid (tretinoin) in the treatment of various stages of xerophthalmia caused by vitamin A deficiency. At the beginning of treatment, rabbits with similar disease in both eyes were given a normal diet and therapeutic doses (25,000 IU) of systemic vitamin A. One eye of each was treated with 0.1% retinoic acid in sesame oil one time per day. The other eye received sesame oil alone. Eyes with moderate disease (advanced keratinization and plaque formation) responded more quickly to topical retinoic acid (clear within three days) than did eyes treated with sesame oil (clear within seven days). No difference in time of response could be observed in corneas with milder or more severe disease (stromal infiltration and corneal vascularization).

Corneal endothelial cell shrinkage after critical point drying.

Corneal endothelial cell densities of 30 rabbit eyes were determined in vivo by specular microscopy and after critical point drying by scanning electron microscopy. The range of shrinkage in area of the cells after critical point drying was 3.6% to 49.1% with a mean of 29.7%. This respresents a linear shrinkage of 1.8% to 28.7% with a mean of 16.4%. Comparisons of endothelial cell size or density between different critical point dried speciments therefore cannot be made without knowing how much shrinkage occurred in each individual specimen.

Xerophthalmia in vitamin A-deficient rabbits. Clinical and ultrastructural alterations in the cornea.

Xerophthalmia developed in the eyes of rabbits maintained on a vitamin A-deficient diet for 4 to 6 months. The earliest clinical change, a lusterless graying of the central corneal epithelium, was noted after 16 to 18 weeks on the diet. Multiple small punctate epithelial erosions appeared in the interpalpebral fissure zone within 7 to 10 days after the lusterless graying became evident. The erosions gradually became confluent, and a striking dry, glazed, peau d'orange appearance was noted. Polycystic microbullae appeared in the epithelium in some eyes. Thick keratinized epithelial plaques developed in all eyes 1 to 2 weeks after the appearance of severe peau d'orange. Electron microscopy of corneas with lusterless graying of the epithelium revealed swelling of the most superficial epithelial cells with flattened and shorter microvillous projections. In corneas with punctate epithelial erosions and keratinized plaques, microvilli were absent or decreased in number on superficial cells, and multilayered, keratinized epithelial cells were present on the surface of the cornea. The stroma appeared essentially normal with minimal edema at all stages when examined by electron microscopy. Intercellular edema was present in the endothelium in early- and late-stage xerotic corneas but could not be detected clinically. No significant clinical or microscopic alterations were seen in the corneas of control rabbits on normal diet or in rabbits on the vitamin A-deficient diet supplemented with vitamin A. The alterations seen in the corneas of vitamin A-deficient rabbits are similar to those which have been described in vitamin A-deficient humans. Rabbit therefore appears to be a good model for further studies of xerophthalmia.

The effects of increased hydrostatic pressure upon normal and regenerated rabbit corneal endothelium.

The effect of increased hydrostatic pressure upon the ability of normal and regenerated endothelium to deturgesce preswollen, de-epithelialized rabbit corneas was studied. Stromal deturgescence occurred as a biphasic response when hydrostatic pressure at the endothelial surface was increased above baseline values. Initially there was a rapid phase of stromal thinning which was dependent upon hydrostatic pressure nad endothelial function. This was followed by a slower phase of corneal thinning which was independent of hydrostatic pressure at the endothelial surface for pressures between 15 and 50 mm Hg. The slow phase of thinning represents the steady-state ability of the endothelium to deturgesce the stroma. Regenerated rabbit endothelium functioned similarly to normal endothelium in deturgescing the stroma. In addition, short-term increases in hydrostatic pressure at the endothelial surface did not produce ultrastructural changes in normal or regenerated corneal endothelial cells.

Corneal endothelial autoradiography with the scanning electron microscope.

A new technique for performing corneal endothelial cell autoradiography with the scanning electron microscope is presented. The scanning electron microscope is able to detect silver grains deposited over tritiated thymidine--labeled nuclei of regenerating corneal endothelium.

Effects of transcorneal freezing on protein content of aqueous humor and intraocular temperature in rabbit and cat.

The effects of transcorneal freezing on protein content of aqueous humor and intraocular temperature at the posterior surface of the cornea, the angle, the iris, and the ciliary processes were determined in rabbits and cats. Normal aqueous protein concentration was 40 +/- 2 mg/dl in rabbits and 43 +/- 4 mg/dl in cats. In rabbits, total aqueous protein content reached its highest level (2790 +/- 302 mg/dl) for 3 hr after transcorneal freezing, decreased by 50% after 4 hr, and was not significantly different than normal at 7 days. In cats, total aqueous protein content also reached its highest level (1610 +/- 290 mg/dl) 3 hr after corneal freezing. Fluctuations occurred thereafter, but protein content was not significantly different from normal after 7 days. The temperature at the corneal endothelium always decreased to below 0 degrees C with a 10 to 25 sec application of the cryoprobe to the cornea in rabbit and cat. Intraocular temperature did not decrease below 24 degrees C at the angle or ciliary processes during application of the cryoprobe for up to 25 sec, whereas the temperature at the pupillary margin of the iris sometimes decreased to near 0 degrees C with a 15 to 25 sec application.

The effects of ketamine sedation and ketamine-pentobarbital anesthesia upon the intraocular pressure of the rabbit.

The effect of ketamine sedation and ketamine-pentobarbital anesthesia upon the intraocular pressure (IOP) of the rabbit was studied by applanation pneumatonography. Peak values of IOP during both ketamine sedation and ketamine-pentobarbital anesthesia were reached 3 to 5 minutes after administration of the drug(s). The peak IOP increase during ketamine sedation (10 mg./kg. IM) was 2.2 +/- 0.4 mm. Hg. The peak IOP increase with ketamine-pentobarbital anesthesia (50 mg./kg. ketamine IM + 30 mg./kg. pentobarbital IM) was 7.1 +/- 0.8 mm. Hg. Atropine premedication did not prevent the increase in IOP seen with ketamine sedation or ketamine-pentobarbital anesthesia.