David T. Ramsey

Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on horse chromosome 6.

BackgroundEquine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. The disease is in agreement with a codominant mode of inheritance in our horse material. Animals presumed to be heterozygous for the mutant allele have cysts originating from the temporal ciliary body, peripheral retina and/or iris. In contrast, animals predicted to be homozygous for the disease-causing allele possess a wide range of multiple abnormalities, including iridociliary and/or peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain horse breed where it occurs at a high frequency among Silver colored horses. The Silver coat color is associated with mutations in PMEL17 that resides on ECA6q23. To map the MCOA locus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for the MCOA locus.ResultsWe performed linkage analysis within 17 paternal half-sib families of the Rocky Mountain horse breed. More than half of the 131 offspring had the Cyst phenotype and about one third had MCOA. Segregation data were obtained by genotyping 10 microsatellite markers most of which are positioned on ECA6q22-23, as well as the missense mutation for the Silver phenotype in PMEL17. Significant linkage was found between the MCOA locus and eight of the genetic markers, where marker UPP5 (Theta = 0, z = 12.3), PMEL17ex11 (Theta = 0, z = 19.0) and UPP6 (Theta = 0, z = 17.5) showed complete linkage with the MCOA locus. DNA sequencing of PMEL17 in affected and healthy control individuals did not reveal any additional mutations than the two mutations associated with the Silver coat color.ConclusionThe MCOA locus can with high confidence be positioned within a 4.9 megabase (Mb) interval on ECA6q. The genotype data on UPP5, PMEL17ex11 and UPP6 strongly support the hypothesis that horses with the Cyst phenotype are heterozygous for the mutant allele and that horses with the MCOA phenotype are homozygous for the mutant allele.

A Survey of ocular abnormalities in Miniature Horses

OBJECTIVE To determine the incidence of ocular abnormalities in miniature horses. DESIGN Descriptive study. ANIMALS STUDIED Fifty-three miniature horses. PROCEDURE Ophthalmic examinations were performed using diffuse and focal illumination, slit-lamp biomicroscopy and indirect ophthalmoscopy. Coat color, mane and tail color, age and gender were recorded with results of ophthalmic examination. RESULTS Ocular abnormalities detected most frequently consisted of cysts arising from the posterior iris, ciliary body, and peripheral retina, curvilinear streaks of retinal pigmented epithelium extending from the peripheral temporal retina, and retinal dysplasia (folds). One miniature horse also had multiple ocular abnormalities (cornea globosa, goniosynechiae, decreased or absent and pupillary light reflexes, miotic and dyscoric pupils, iris hypoplasia, and epinuclear cataract). Ocular abnormalities were observed in horses that had a flaxen or white mane and tail color and a chocolate coat color. CONCLUSIONS Abnormal ocular phenotype detected in eyes of Miniature Horses was similar to multiple congenital and hereditary ocular abnormalities reported in the Rocky Mountain Horse. Phenotypic ocular developmental abnormalities and coat, mane and tail color were most compatible with a heterozygous or homozygous effect of the Silver Dapple locus.

Feline Chlamydia and Calicivirus Infections

Feline conjunctivitis is common and often presents a clinical challenge to the veterinarian. Chlamydia psittaci is an important pathogen and should always be considered when evaluating cats with conjunctivitis. FCV is an infrequent cause of conjunctivitis and only causes the disease in conjunction with other clinical signs of this infection, such as oral mucosal ulcers and upper respiratory tract disease.

Primary Adenocarcinoma of the Gland of the Nictitating Membrane in a Cat

An 11-year-old, neutered, male domestic shorthair was presented with a five-month history of recurrent, unilateral, seromucoid discharge from the right eye. A verrucous mass extended from the posterior aspect of the nictitating membrane. Adenocarcinoma of the gland of the nictitating membrane (GNM) was diagnosed upon biopsy. The cat subsequently developed metastases to the lungs, pleura, mediastinum, liver, and kidneys and died six months after clinical signs first were observed. Little is known about the biological behavior of adenocarcinoma of the GNM in cats. This is the first report that describes the natural progression of this disease.

A partial gene deletion of SLC45A2 causes oculocutaneous albinism in doberman pinscher dogs

The first white Doberman pinscher (WDP) dog was registered by the American Kennel Club in 1976. The novelty of the white coat color resulted in extensive line breeding of this dog and her offspring. The WDP phenotype closely resembles human oculocutaneous albinism (OCA) and clinicians noticed a seemingly high prevalence of pigmented masses on these dogs. This study had three specific aims: (1) produce a detailed description of the ocular phenotype of WDPs, (2) objectively determine if an increased prevalence of ocular and cutaneous melanocytic tumors was present in WDPs, and (3) determine if a genetic mutation in any of the genes known to cause human OCA is causal for the WDP phenotype. WDPs have a consistent ocular phenotype of photophobia, hypopigmented adnexal structures, blue irides with a tan periphery and hypopigmented retinal pigment epithelium and choroid. WDPs have a higher prevalence of cutaneous melanocytic neoplasms compared with control standard color Doberman pinschers (SDPs); cutaneous tumors were noted in 12/20 WDP (<5 years of age: 4/12; >5 years of age: 8/8) and 1/20 SDPs (p<0.00001). Using exclusion analysis, four OCA causative genes were investigated for their association with WDP phenotype; TYR, OCA2, TYRP1 and SLC45A2. SLC45A2 was found to be linked to the phenotype and gene sequencing revealed a 4,081 base pair deletion resulting in loss of the terminus of exon seven of SLC45A2 (chr4∶77,062,968-77,067,051). This mutation is highly likely to be the cause of the WDP phenotype and is supported by a lack of detectable SLC45A2 transcript levels by reverse transcriptase PCR. The WDP provides a valuable model for studying OCA4 visual disturbances and melanocytic neoplasms in a large animal model.

A new inherited ocular anomaly in pigmented White Leghorn chickens

Inherited ocular anomalies in chickens include several types of microphthalmia, retinal dysplasia, retinal degeneration, cataract, buphthalmos and pop-eye, or keratoconus in White Leghorns.2–5,7,8,12,15–18 In this report, a new ocular anomaly that appeared in pigmented White Leghorns homozygous for a mutation at the dominant white (I) locus is described with emphasis on clinical, gross, and histologic findings to aid in the diagnosis of the ocular lesions. An incompletely dominant mutation, called Smoky Joe (SJ), allows the production of feather pigment, which the I allele inhibits. The SJ mutation originally appeared in ADOL Line 0, a noninbred White Leghorn line maintained at the USDA Avian Disease and Oncology Laboratory (ADOL) in East Lansing, Michigan. Females homozygous for SJ have dark grey feathers with barring and homozygous males have much lighter colored plumage. This dimorphism in color is the result of the dilution that occurs with two copies of sexlinked barring in the males. The plumage of heterozygous birds (I, SJ) is intermediate in color compared to either parental type. Phthisis bulbi was noticed in adult females of the second generation of the homozygous SJ population. None of the parents of these females had apparent ocular lesions. Approximately 30% of the 85 surviving females had phthisis bulbi, while none of the 100 surviving males were affected. There was no clinical evidence of bacterial or viral infection, and the chickens were housed in pens isolated from chickens with experimental viral infections. Because the ocular anomaly appeared to be recessive and sex-linked, 4 test matings were designed to further study the inheritance. In matings 1 and 2, sighted SJ males, which were suspected of being carriers of the syndrome, were mated to either affected or sighted SJ females. These same male birds were then mated to either sighted females of Line 0 (II) (mating 3) or sighted females of ADOL Line 15I5 (II) and Line 0 (II) (mating 4). All chicks had ophthalmic examinations at hatch and 2, 4, and 8 weeks of age. In mating 1,197 chicks were examined. Of the females, 62% were affected, and 10% of the males were affected.

Whorl pattern keratopathies in veterinary and human patients

The course travelled by corneal epithelial cells from their stem cell niche at the limbus toward the vertex of the cornea is normally not evident due to their transparency, but in certain conditions, the epithelial cells can be rendered visible to the clinician. In such cases, the pathway taken by epithelial cells can manifest as a whorl pattern described using a variety of terms including hurricane keratitis/keratopathy, vortex keratopathy, whorl keratopathy, cornea verticillata, and at times, named after causative agents as exemplified by amiodarone keratopathy. Here, we briefly discuss the terminology used and the spectrum of conditions that can result in keratopathies with whorl patterns in human patients. We review the manifestations of such patterns in veterinary patients and discuss the state of understanding of the underlying forces that create the whorl distribution of epithelial cells on the ocular surface.

A quantitative assessment of TPP-induced delayed neuropathy in the retina and lateral geniculate nucleus of the European ferret (Mustela putorius furo).

Triphenyl phosphite (TPP) has been examined extensively in our lab to assess its degenerative effects on the visual pathway of the European ferret. Tanaka et al. [Fundam. Appl. ToxicoL 22 (1994) 577; J. Toxicol. Environ. Health 58 (1999) 215] reported an age-related pattern of fiber and cell body degeneration progressing from retinal axons and lateral geniculate nucleus (LGN) neurons to the visual cortex. These studies, however, did not address whether TPP exposure results in retinal ganglion cell (RGC) degeneration, nor did they quantify the degenerative effects in the LGN. The purpose of this study was to quantify the effects of TPP on RGCs and LGN neurons. We administered single subcutaneous injections of TPP (1184 mg/kg) to 13 ferrets for histological analysis. The retinae were examined as whole-mounts and the brains sectioned parasagittally (50 microm). RGC countsfrom matched areas of nasal retina showed significantly fewer (21%) neurons in the TPP-treated ferrets (Sd = 282 +/- 52S.D.; 7d = 284 +/- 12S.D.) compared with control (359 +/- 42S.D.). No significant difference in cell number was found in temporal retina, even though this region contained, on average, 13% fewer ganglion cells in TPP-treated ferrets (Sd = 3344 +/- 44S.D.; 7d = 357 +/- 39S.D. versus control = 394 +/- 72S.D.). The mean soma sizes and RGC cell size distributions for nasal and temporal retinae were not significantly different for any group. LGN neurons were significantly smaller (28%) than control in the TPP-treated ferrets (Sd = 155 microm2 +/- 23S.D.; 7d = 152 microm2 +/- 28S.D. versus control = 214 microm2 +/- 9S.D.). Cell size distributions for LGN neurons were shifted toward smaller cell sizes in both TPP-treated groups compared to control.