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Objective: To determine the extent of fluctuation in circadian intraocular pressure (IOP) and the efficacy of topical dorzolamide 2% q 8 h in lowering IOP and blunting circadian fluctuation in IOP in glaucomatous cats., Animals Studied: Seven adult cats with primary congenital glaucoma (PCG)., Procedures: Measurements of IOP and pupil diameter were obtained for both eyes (OU) of each cat q 4 h for 12 days. Cats were housed in a laboratory animal facility with a 12-h light:dark cycle. Baseline values were established for 2 days. For the next 5 days, placebo (1.4% polyvinyl alcohol) was administered OU q 8 h. Dorzolamide 2% was then administered OU q 8 h for a further 5 days. A multivariate mixed linear model was fitted to the data, with parameters estimated from a Bayesian perspective. The 4 am time point was selected as the reference for the purposes of comparisons., Results: Estimated mean IOP for the reference time point pre-treatment was symmetric (about 33 mmHg OU). In all cats, IOP was significantly lower during the diurnal phase, relative to the 4 am measurements, with highest IOP observed 2-6 h after the onset of the dark phase. Circadian fluctuations in IOP were dampened during the treatment period. There was a significant decrease in IOP in all cats during the dorzolamide treatment period (estimated mean for the treatment period reference = 17.9 mmHg OU)., Conclusions: Topical dorzolamide 2% q 8 h is effective in reducing IOP and IOP fluctuation in cats with PCG., (© 2011 American College of Veterinary Ophthalmologists.)

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by loss of activity of α-l-iduronidase and attendant accumulation of the glycosaminoglycans dermatan sulfate and heparan sulfate. Current treatments are suboptimal and do not address residual disease including corneal clouding, skeletal deformities, valvular heart disease, and cognitive impairment. We treated neonatal dogs with MPS I with intravenous recombinant α-l-iduronidase replacement therapy at the conventional 0.58 mg/kg or a higher 1.57 mg/kg weekly dose for 56 to 81 weeks. In contrast to previous results in animals and patients treated at a later age, the dogs failed to mount an antibody response to enzyme therapy, consistent with the induction of immune tolerance in neonates. The higher dose of enzyme led to complete normalization of lysosomal storage in the liver, spleen, lung, kidney, synovium, and myocardium, as well as in the hard-to-treat mitral valve. Cardiac biochemistry and function were restored, and there were improvements in skeletal disease as shown by clinical and radiographic assessments. Glycosaminoglycan levels in the brain were normalized after intravenous enzyme therapy, in the presence or absence of intrathecal administration of recombinant α-l-iduronidase. Histopathological evidence of glycosaminoglycan storage in the brain was ameliorated with the higher-dose intravenous therapy and was further improved by combining intravenous and intrathecal therapy. These findings argue that neonatal testing and early treatment of patients with MPS I may more effectively treat this disease.

Purpose: To characterize the timing and extent of functional recovery in healthy canine eyes exposed to acute elevation of intraocular pressure (IOP)., Methods: Acute elevation of IOP was induced in 14 healthy Beagles by elevating IOP above the levels of systolic blood pressure for 60 min (average elevation was between 100 and 160 mmHg). Menace, dazzle and pupillary light reflexes (PLR) were tested at 1, 7, 14 and 28 days post elevation. Optical coherence tomography was used to evaluate retinal thickness preoperatively and at 15 and 30 days post elevation., Results: One day post elevation all animals were blind in the operated eye (no positive menace), 5/14 had positive PLR and 10/14 had positive dazzle response. Seven days post elevation 4/14 animals had positive menace response and all animals (14/14) had positive dazzle and PLR responses. Fourteen and 28 days post elevation all animals had positive menace, PLR and dazzle responses. Optical coherence tomography analysis revealed significant thinning of the inferior retina (pre elevation: 156.3 +/- 4.8 microm; 15 days post elevation: 125 +/- 10.4 microm; 30 days post elevation 123 +/- 11.9 microm; P < 0.01, anova). The superior retina, however, did not show any detectable decrease in thickness compared to control eyes (pre elevation: 193.8 +/- 2.6 microm; 15 days post elevation: 176.9 +/- 8.5 microm; 30 days post elevation 176.9 +/- 7 microm; P = 0.057, anova)., Conclusions: Detailed functional and morphologic analysis revealed precise information about retinal damage after acute elevation of IOP. Canine retina has the capacity to recover at least some visual function even at 14 days after acute elevation of the IOP. More aggressive medical and surgical treatment of canine glaucomatous patients may be indicated despite complete loss of visual function, PLR and dazzle responses in early days after development of an acute glaucomatous attack.

Purpose: The goal of this study was to describe the detailed localization of the novel oxygen-binding molecules, neuroglobin (Ngb) and cytoglobin (Cygb), in mammalian retinas and to determine whether Ngb and Cygb are neuronal or glial proteins in the retina., Methods: Antibodies directed against Ngb and Cygb were used to examine their patterns of distribution in normal canine retinas. Immunoblot analysis was performed to verify antibody specificity and the presence of Ngb and Cygb in canine tissues. Double-labeling immunohistochemistry was performed with the Ngb and Cygb antibodies along with antibodies against neuronal (MAP-2, class III beta-tubulin (TUJ1), PKCalpha, and calretinin) and glial antigens (vimentin and CRALBP). Tissue sections were analyzed with light and confocal microscopy., Results: Ngb and Cygb proteins were observed in different retinal cells. Cygb (but not Ngb) was also present in canine kidney, liver, lung, and heart tissue. Immunohistochemical analysis of canine retinas demonstrated Ngb immunoreactivity (IR) in the ganglion cell layer (GCL), inner (INL) and outer (ONL) nuclear layers, inner (IPL) and outer plexiform (OPL) layers, photoreceptor inner segments (IS), and retinal pigment epithelium (RPE). Ngb IR was localized within retinal neurons, but not in glia. Cygb IR was found in neurons and their processes in the GCL, IPL, INL, and OPL and within the RPE, but not in glia., Conclusions: Ngb and Cygb are widely distributed in retinal neurons and RPE, but not in glial cells of the canine retina. Their structure and distribution is suggestive of a possible role in oxygen transport in the mammalian retina.

Case Description: A 7-year-old Siberian Husky-type dog with heterochromia irides was evaluated because of signs of pain associated with the right eye., Clinical Findings: Unilateral panuveitis, iris bombé, and secondary glaucoma were detected in the right eye. Tear production was low bilaterally. Facial and truncal poliosis and vitiligo were also evident; skin biopsy specimens were obtained from the nasal planum. Uveodermatologic syndrome was diagnosed on the basis of histopathologic findings of a lichenoid interface dermatitis and pigmentary incontinence within the dermis. Immunohistochemical analysis was performed on skin samples retrospectively, and findings were inconclusive., Treatment and Outcome: Treatment involved topical (ocular) and oral administration of corticosteroids, oral administration of azathioprine, and topical (ocular) administration of a carbonic anhydrase inhibitor and a lacrimostimulant. The secondary glaucoma was refractory to treatment, and the right eye was enucleated. Uveodermatologic syndrome was confirmed via histologic examination of ocular tissues. The left eye remained free of inflammation 16 months after the initial diagnosis. The periocular skin and skin of the nose partially regained pigment, but the hair did not., Clinical Relevance: Some breeds in which uveodermatologic syndrome has been reported (eg, Siberian Huskies, Old English Sheepdogs, Australian Shepherds, and Shetland Sheepdogs) often have heterochromia irides. This case highlights the fact that dogs with asymmetric uveal pigmentation may have unilateral ocular changes; therefore, uveodermatologic syndrome should not be excluded as a differential diagnosis on the basis of unilateral clinical signs.

Purpose: To develop an inducible mouse model of glaucoma., Methods: An obstruction of aqueous humor outflow in adult C57BL6/J mice was induced by combined injection of indocyanine green (ICG) dye into the anterior chamber and diode laser treatment. To evaluate intraocular pressure (IOP), tonometry was performed with a modified Goldmann tonometer. The function of the retina was evaluated with electroretinography (ERG)., Results: IOP was significantly elevated in surgical eyes compared with control eyes: before surgery, 15.2 +/- 0.6 mm Hg; 10 days after surgery, 33.6 +/- 1.5 mm Hg (P < 0.001); and 30 days after surgery, 27.4 +/- 1.2 mm Hg (P < 0.001). However, 60 days after surgery, IOP in the surgical eyes decreased to 19.5 +/- 0.9 mm Hg and was not significantly different compared with control eyes (control, 17.3 +/- 0.7 mm Hg; P = 0.053). ERG amplitudes, expressed as a ratio (surgical/control), were decreased in surgical eyes. The amplitudes for b-wave were: before surgery, 107.6% +/- 4.6%; 28 days after surgery, 61% +/- 4% (P < 0.001); and 56 days after surgery, 62% +/- 5.6% (P < 0.001). Oscillatory potentials were the most dramatically affected: before surgery, 108.6% +/- 6.7%; 28 days after surgery, 57.5% +/- 5% (P < 0.01); and 56 days after surgery, 57% +/- 8.5% (P < 0.001). Amplitudes of the a-waves had relatively smaller but still significant deficits: before surgery, 105.8% +/- 6.9%; 28 days after surgery, 72.2% +/- 5.4% (P < 0.01); and 56 days after surgery, 79.8% +/- 11.0% (P < 0.01). Histologic analysis of the surgical eyes revealed development of anterior synechia, loss of retinal ganglion cells (RGCs), and thinning of all retinal layers. Electron microscopy of optic nerve cross sections revealed swelling and degeneration of the large diameter axons and gliosis., Conclusions: Diode laser treatment of ICG saturated episcleral veins causes a chronic elevation of IOP and sustained ERG deficits.

Purpose: To evaluate visual function in rats with chronic elevation of intraocular pressure (IOP)., Methods: Chronic ocular hypertension was induced in the left eye of 14 adult Brown Norway rats by cauterizing 3 vortex veins and 2 major episcleral veins; the right eye served as a non-operated control. A control group (n=5) was sham operated on the left eye. Prior to surgery, the IOP was measured with a Tonopen, the pupil light reflex (PLR) evaluated with a custom-made computerized pupillometer and electroretinograms (ERGs) were recorded simultaneously from both eyes post surgically: IOP was measured on weeks 1, 3, 5 and 8 post-operatively, pupil light reflexes on weeks 1, 4 and 8 post-operatively, and ERGs on weeks 4 and 8 post-operatively. Sixty five days postoperatively, rats were euthanized and optic nerves and eye globes were prepared for histological analysis., Results: Seven days after surgery 5/14 rats developed significant elevation of the IOP in operated eyes (control eyes: 25.1+/-0.5mmHg; operated eyes: 34.1+/-0.6mmHg; mean+/-SEM; p=0.0004; Paired t-test). Elevation of the IOP was sustained at 3 (p=0.002) and 5 (p=0.007) weeks postoperatively. However, IOP values did not significantly differ between control and operated eyes 8 weeks postoperatively (p=0.192, Paired t-test). Sham operated animals showed no elevation of the IOP 7 days postoperatively. When the ratio between consensual and direct PLR (PLR(ratio)=consensual/direct PLR; pupil of unoperated eye recorded) was examined in rats which developed elevation of the IOP, preoperative values were 92.2+/-4% (mean+/-SEM), 1 week postoperatively 65+/-4% (significantly different from preoperative values, p<0.05 Repeated Measures ANOVA with Dunnett's Multiple Comparison test, n=5), 4 weeks postoperatively 60.6+/-3.2% (p<0.01, n=5). By 8 weeks postoperatively, pupil responses had essentially recovered 75.4+/-6.9% (p>0.05, n=5). Rats whose IOP values did not rise after surgery and sham operated rats did not develop pupil deficits 4 weeks postoperatively. Rats with elevated IOP displayed a significant decrease in ERG amplitudes in operated eyes at 4 weeks (a-wave(operated)/a-wave(control) (a-wave ratio)=42+/-14% (mean+/-SEM); b-wave(operated)/b-wave(control) (b-wave ratio)=43+/-16%) but not at 8 weeks postoperatively (a-wave ratio=88+/-8.4%; b-wave ratio=82.9+/-9%). Sham operated and rats whose IOP values remained non-elevated after surgery did not develop ERG deficits 4 weeks after surgery. Histological analysis did not reveal any damage in the eyes of animals with elevated intraocular ocular pressure with the exception of one rat, which still had ERG and pupil deficits at the end of experiment., Conclusions: Development of ERG and PLR deficits are proportional to the elevation of the IOP in the rat model of chronic ocular hypertension. Functional monitoring of the ERG and PLR are useful objective techniques for the detection of retina and optic nerve deficits.

Purpose: To characterize the pupil light reflex (PLR), electroretinographic (ERG) and tonometric parameters which might be of importance for the in vivo characterization of mouse models of chronic ocular hypertension., Methods: C57/BL6 mice were used for experiments. The PLR was evaluated with a computerized pupillometer (n = 14), ERGs were recorded simultaneously from both eyes (n = 23) and IOP was measured with a modified Goldmann tonometer (n = 23)., Results: The analysis of the PLR parameters confirmed the consensual PLR did not have significantly different amplitude (p > 0.1) and latency time (p > 0.1) compared to the direct PLR. However, PLR velocity (p = 0.004) was significantly smaller in the consensual PLR. Electroretinography revealed a-wave amplitude of 168.3 +/- 9.6 microV with latency of 27.5 +/- 0.6 ms and b-wave 403 +/- 28.8 microV with latency of 22.7 +/- 0.6 ms. The flicker ERG recording revealed amplitudes of 20.6 +/- 2.4 microV. Tonometry experiments revealed that modified Goldmann tonometer measurements correlated well with invasive manometry (r(2) = 0.89). The mean IOP of the mouse was 15.3 +/- 0.6 mmHg., Conclusions: Consensual PLR in mice is relatively slower than the direct PLR, but retains the same degree of constriction comparing to the direct PLR. A modified Goldmann tonometer seems to be a reliable non-invasive tool for IOP measurements in mice.

OBJECTIVE: The goal of this project was to explore the possibility that fungal organisms produce metabolites that inhibit angiogenesis. Procedures Fungal cultures were obtained from cases of keratomycosis, grown in Sabouraud's dextrose broth, and sterile filtered for use in experiments. The Matrigel assay was used to screen the filtrate samples for antiangiogenic activity. Matrigel is a basement membrane matrix that supports the differentiation of human umbilical vein endothelial (HUVE) cells into a capillary-like network of tubules. HUVE cells were cultured using standard techniques and passaged at confluence, with all cells being used at passage 3-6. HUVE cells (40 000 cells) were pipetted into each well of a 24-well tissue-culture plate coated with Matrigel. An aliquot of fungal media filtrate was added to each well and the plates allowed to incubate for 18 h, at which time they were evaluated for tubule formation. RESULTS: Two fungal isolates showed inhibition of tubule formation. The addition of 100, 200 and 400 &mgr;L of the fungal media filtrate from the first isolate (Fusarium sp. 99A34574) produced a consistent and dose-dependent inhibition of tubule formation. The second isolate (Aspergillus sp. 271599) did not show inhibition of tubule formation with 100 or 200 &mgr;L added to the wells, however, it did show inhibition at 400 &mgr;L/well. The remaining three isolates did not cause inhibition at any concentration. CONCLUSIONS: Our findings suggest that certain fungal organisms produce metabolites that inhibit tubule formation in vitro, and that these metabolites may play a significant role in altering the host vascular response to fungal infections of the cornea.

Swab specimens for fungal isolation were collected from the healthy conjunctival sacs of 3 species of captive camelids (Lama glama, L guanicoe, L pacos) and llama-guanaco hybrids. Fungi were collected from over half the animals in winter (53%) and summer (56%). Fungal species of 10 genera were isolated. In both seasons, Aspergillus was the most commonly isolated genus; at least 9 species of Aspergillus were found. The fungal organisms isolated were similar to those found in healthy eyes of other domestic animals and may represent a random seeding from the environment where they are ubiquitous.

Healthy conjunctival sacs of 88 animals of 3 species of captive camelids (Lama glama, Lama guanicoe, Lama pacos) and llama-guanaco hybrids were sampled for bacterial and mycoplasmal flora. Mycoplasmas were not isolated from any animal. Eleven genera of bacteria were isolated. The most frequent isolates were Staphylococcus epidermidis and Pseudomonas spp. Nine varieties of Pseudomonas were found, which represented at least 3 Pseudomonas species. Many of the bacterial isolates (especially the pseudomonads) are potential pathogens in the eyes of these camelids.

A primary pulmonary bronchogenic adenocarcinoma originating from an intramediastinal accessory lung was diagnosed in a 14.5-year-old cat. The cat had been admitted because of a cloudy right eye. Physical examination revealed a thin cat with severe iritis, aqueous flare, and a fibrin clot in the anterior chamber of the right eye. Right fundic examination revealed bullous retinal detachment superior to the optic disc. Euthanasia and necropsy were requested when FeLV test results were positive. Metastatic neoplastic cells similar to those of the primary tumor were detected in the choroid, ciliary body, and ciliary processes of the right eye. Ciliary and iridic stromal necrosis attributable to neoplastic embolization of uveal vessels had led to severe uveitis. Foci of metastasis were also in the heart, kidney, and cerebral meninges.

Intravenous injection of xylazine (0.01-1 mg/kg) produced a dose-dependent mydriasis associated with a depression of tonic ciliary nerve activity in anesthetized cats. Xylazine-induced mydriasis was apparent in the sympathectomized iris but was absent in the parasympathectomized, physostigmine-treated iris. Epinephrine (30 micrograms/kg, i.v.) produced a slightly greater mydriasis in the sympathectomized iris than in the parasympathectomized, physostigmine-treated iris. The alpha 2-adrenergic blocking agent, yohimbine (0.5 mg/kg, i.v.) antagonized the pupillary dilation and reversed the depression of ciliary nerve activity induced by xylazine administration. In rats pretreated with reserpine (7.5 mg/kg, s.c., 20 h) and alpha-methyl-p-tyrosine (250 mg/kg, i.p., 5 h), intravenous injection of xylazine (0.01-1 mg/kg) resulted in mydriasis of similar magnitude as control animals. However, xylazine induced bradycardia in the control group but not in the pretreated animals. The results suggest that pupillary dilation produced by i.v. xylazine is primarily the result of a central inhibition of parasympathetic tone to the iris. It also appears that xylazine produces this effect via postsynaptic alpha 2-adrenergic mechanisms, while it produces bradycardia through a presynaptic alpha 2-adrenergic mechanism.

Pupillary response to xylazine (10-300 micrograms/kg, i.v.) norepinephrine (1-30 micrograms/kg. i.v.) and atropine (3-100 micrograms/kg, i.v.) were observed in rats anaesthetized with pentobarbital. Xylazine caused a dose-dependent mydriasis which was antagonized by a selective alpha 2-adrenergic blocking agent, yohimbine (2.5 mg/kg, i.v.). was less effective in antagonizing this effect of xylazine. A selective alpha 1-adrenergic blocking agent, prazosin (2.5 mg/kg, i.v.) was ineffective in reducing the xylazine-induced mydriasis. In contrast, both phentolamine and prazosin blocked the pupillary dilation produced by norepinephrine, while yohimbine was much less effective in antagonizing norepinephrine-induced mydriasis. Atropine also induced a dose-dependent mydriasis which was not affected by yohimbine pretreatment. The present study suggests that the mydriatic effect of xylazine in the rat is mediated by an adrenergic mechanism, possibly by stimulating the alpha 2-adrenergic receptors in the iris and CNS.

A 9-year-old dog with a 2-month history of weight loss and a 1-week history of blindness had an IgA-forming myeloma. Seemingly, the blindness was a result of bilaterally detached retinas. The dog also had leukopenia, anemia, hypoalbuminemia, hyperglobulinemia, and proteinuria as well as lytic lesions in the cervical portion of the spine and high IgA concentrations in serum and urine. Evaluation of aspirates from the subretinal spaces revealed lymphocytes in a proteinaceous fluid. Histologically, retinal lesions consisted of vascular endothelial cell damage and intraretinal cysts and hemorrhages.