Medical and surgical management of the glaucoma patient.

Glaucoma usually causes rapid blindness in small animals and should be treated as a true ophthalmic emergency. Current treatment is directed toward decreasing intraocular pressure to protect the optic nerve and preserve vision. These treatment methods include various medical and surgical methods that are often combined for a particular patient. No magic drugs or surgeries exist to permanently control glaucoma; the clinician often has to switch to assorted methods of treatment after the previous treatments fail to control the intraocular pressure. Newer theories on the cause of glaucoma involve various vascular and toxic effects on the optic nerve rather than simple mechanical damage to the nerve from increased ocular pressure. Therefore, treatments designed to protect the optic nerve from biochemical alterations are probably the future of treating this challenging disease.

Transcriptional regulation of the Bmp2 gene. Retinoic acid induction in F9 embryonal carcinoma cells and Saccharomyces cerevisiae.

Bmp2, a highly conserved member of the transforming growth factor-beta gene family, is crucial for normal development. Retinoic acid, combined with cAMP analogs, sharply induces the Bmp2 mRNA during the differentiation of F9 embryonal carcinoma cells into parietal endoderm. Retinoic acid (RA) also induces the Bmp2 gene in chick limb buds. Since normal Bmp2 expression may require an endogenous retinoid signal and aberrant Bmp2 expression may cause some aspects of RA-induced teratogenesis, we studied the mechanism underlying the induction of Bmp2. Measurements of the Bmp2 mRNA half-life and nuclear run-on assays indicated that RA stimulated the transcription rate of the Bmp2 gene. The results of ribonuclease protection and primer extension assays indicated that Bmp2 transcription started 2,127 nucleotides upstream of the translation start site in F9 cells. To identify genetic elements controlling this transcription rate increase, upstream and downstream genomic sequences flanking the Bmp2 gene were screened using chloramphenicol acetyltransferase reporter genes in F9 cells and beta-galactosidase reporter genes in Saccharomyces cerevisiae that were cotransformed with retinoic acid receptor and retinoid X receptor expression plasmids. RA-dependent transcriptional activation was detected between base pairs -2,373 and -2,316 relative to the translation start site. We also identified a required Sp1 binding site between -2,308 and -2,298. The data indicate that Bmp2 is directly regulated by retinoic acid-bound receptors and Sp1.

Modulation of proteolytic activity associated with persistent corneal ulcers in dogs.

Canines affected with corneal lesions demonstrate increased proteolytic activity at the affected site. Canines that develop persistent corneal ulcers and maintain elevated levels of proteolytic activity respond to protease inhibitor therapy with polysulpated glycosaminoglycan, PSGAG. In this study, the proteolytic activity expressed in lacrimal fluid of canines was evaluated as normal (1.15 U mL-1) or healed (1.19 U mL-1). Six of the 26 dogs affected with persistent corneal ulcers, however, had a protease level consistent with the unaffected control animals. These dogs did not appear to respond to PSGAG therapy. Two pathophysiologies for persistent corneal ulcers are indicated. Identifying which mode is active could help determine the therapeutic treatment needed.

Topical administration of cyclosporine for treatment of keratoconjunctivitis sicca in dogs.

Sixty dogs with chronic keratoconjunctivitis sicca were treated by topical administration of 2% cyclosporine twice daily. Causes and duration of keratoconjunctivitis varied. Tear production improved in 75 of 100 eyes, and corneal pigmentation decreased in 45 of 67 eyes. Six factors were evaluated to determine their influence on treatment outcome. The only significant variable was the initial Schirmer tear test value. Side effects were few. Evidence of burning in response to application of cyclosporine resolved with change in the formulation of the topical solution.

Angiotensin converting enzyme system in the normal canine eye: pharmacological and physiological aspects.

The function of the renin-angiotensin-aldosterone system (RAAS) in the mammalian eye remains unclear, although alterations in the concentrations of various pathway components can influence intraocular pressure and the electroretinogram. Angiotensin Converting Enzyme (ACE) has been localized to ocular tissues and fluids. Aqueous humor and serum values of ACE are increased in sarcoid uveitis patients. We used the dog to simultaneously examine the effects of a topically administered ACE inhibitor on the intraocular pressure (IOP), on components of the renin-angiotensin pathway in the serum and aqueous humor, and to monitor any systemic effects of the ACE inhibitor. The novel ACE inhibitor, SCH 33861 (Schering Corporation), decreased IOP in amounts similar to timolol when applied topically to the canine eye. Serum ACE values significantly decreased in SCH 33861 treated dogs, while aqueous ACE values were only slightly decreased. A decrease in heart rate, and systolic and diastolic blood pressure in these dogs during the treatment period indicated probable systemic absorption. Normal values of aqueous humor and serum angiotensin-I were established for the dog. Plasma renin activity and angiotensin-I values were not significantly changed for any of the treatment groups. Topical application of SCH 33861 to the canine eye is a useful model to further evaluate the role of the renin-angiotensin system in the eye.

Evaluation of the Schirmer tear test in clinically normal rabbits.

Mean (+/- SD) value for results of the Schirmer tear test without use of topical anesthesia on 142 rabbit eyes was 5.30 (+/- 2.96) mm/min; range was 15 mm/min, with low value of 0 and high value of 15 mm/min. Two SD from the mean provided a normal clinical range of 0 to 11.2 mm/min for inclusion of 95% of the population. Significant differences were not evident between eye (right vs left) or gender or among breeds; interaction among eye, gender, and breed also was not observed. Although mean values for 2 breeds were significantly different from values in the other 10 breeds and from each other, they were still within the proposed normal range of 2 SD. The Schirmer tear test without topical anesthesia may be useful in rabbits for evaluation of increased values correlated with ocular irritation, rather than for determination of decreased values associated with keratoconjunctivitis sicca.

Bilateral trigeminal nerve paralysis and Horner's syndrome associated with myelomonocytic neoplasia in a dog.

A 5-year-old male Doberman Pinscher had nasal stenosis, dropped mandible, bilateral atrophy of masseter and temporalis muscles, and Horner's syndrome caused by aleukemic myelomonocytic leukemia. Neoplastic cellular neurotropism, diffuse turbinate and nodular peribronchial infiltrate, and a hepatic portal infiltrative pattern similar to that of lymphoma were microscopic features of interest.

Hypocalcemia associated with administration of sodium bicarbonate for salicylate intoxication in a cat.

Hypocalcemia was believed to be the result of aggressive sodium bicarbonate treatment for a cat with aspirin intoxication. The cat developed progressive neuromuscular tetany during the bicarbonate treatment and was determined to have a low serum ionized calcium value.