Bret A. Moore

Identification of genetic elements in metabolism by high-throughput mouse phenotyping.

Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of co-regulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome.The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS.

Clinical findings and normative ocular data for free‐living Anna's (Calypte anna) and Black‐chinned (Archilochus alexandri) Hummingbirds

OBJECTIVEnTo estimate the prevalence of ocular disease and obtain normative ocular data for free-living hummingbirds.nnnANIMALS STUDIEDnTwo hundred and sixty-three free-living, adult Hummingbirds from coastal and inland central California were studied, including Annas (Calypte anna, n = 186) and Black-chinned (Archilochus alexandri; n = 77) hummingbirds.nnnPROCEDURESnSlit lamp biomicroscopy and indirect ophthalmoscopy were performed on all individuals. Rebound tonometry, measurement of horizontal palpebral fissure length, and streak retinoscopy were performed on select individuals. Five conscious Annas Hummingbirds underwent ocular imaging including fundus photography, digital slit lamp photography, and anterior segment and retinal optical coherence tomography.nnnRESULTSnThe prevalence of ocular disease in this population was 2.28%. Ocular imaging revealed a thin cornea, shallow anterior chamber, large lens, and a single central, deep convexiclivate fovea. Mean ± SD intraocular pressure was 11.21 ± 2.23 mm Hg. Mean ± SD eyelid length was 2.59 ± 0.19 mm. All eyes were emmetropic or mildly hyperopic with a mean (range) ± SD refractive error of +0.32 (-0.25 to +1) ± 0.33 diopters.nnnCONCLUSIONSnConsistent with previous reports, these data suggest that hummingbirds have visual characteristics found in predatory and prey species, as well as a low prevalence of spontaneous ocular disease. This work provides a set of reference values and clinical findings that can be used in the future research on hummingbird vision and ocular disease. It also provides representative diagnostic images of normal birds and demonstrates that advanced ocular imaging can be performed on manually restrained hummingbirds without pharmacologic dilation.

Doppler ultrasonography of the pectinis oculi artery in harpy eagles ( Harpia harpyja )

Twenty harpy eagles (Harpia harpyja) without systemic or ocular diseases were examined to measure blood velocity parameters of the pectinis oculi artery using Doppler ultrasonography. Pectinate artery resistive index (RI) and pulsatility index (PI) were investigated using ocular Doppler ultrasonography. The mean RI and PI values across all eyes were 0.44±0.10 and 0.62±0.20 respectively. Low RI and PI values found in the harpy eagle´s pectinis oculi artery compared with the American pekin ducks one and other tissue suggest indeed a high metabolic activity in pecten oculi and corroborates the hypothesis of a nutritional function and/or intraocular pressure regulation.

Lipoidal corneal degeneration in aged falcons

OBJECTIVEnTo present a case series of idiopathic lipoidal corneal degeneration in falcons.nnnANIMALS STUDIEDnFive falcons including three peregrine falcons (Falco peregrinus), one prairie falcon (Falco mexicanus), and one red-naped shaheen (Falco peregrinus babylonicus) were observed to develop slowly progressive corneal opacification that began at the temporal limbus and extended centripetally across the cornea over a period of years. Four of the birds were over 20xa0years old.nnnPROCEDURESnAll animals underwent complete ophthalmic examinations. A red-naped shaheen underwent ocular imaging via spectral-domain optical coherence tomography. Two peregrine falcons were euthanized due to declining health, and their eyes were examined histologically.nnnRESULTSnThe opacities were pale and granular, with frequent vascularization associated perilimbally. Diffuse neutral lipid was observed in stromal cells throughout the corneal stroma of both clear and opaque areas of the cornea, sparing only the acellular anterior limiting lamina. Clusters of cholesterol crystals surrounded by macrophages were present in the mid-stroma. Fibrosis was evident in a subepithelial location, which separated the epithelium from the anterior limiting lamina. Ultrastructurally, diffuse vacuolization of the keratocytes was observed. No other ophthalmic or systemic abnormalities were noted.nnnCONCLUSIONSnResults suggest that lipid degeneration occurs rarely in captive falcons of advanced age. The underlying cause is unclear. Though unsubstantiated, possible contributing factors include dyslipoproteinemia, corneal trauma, diet, and age-related alterations in corneal metabolism. The initiation of pathology at the temporal limbus, as well as slow progression, suggests that exposure contributes to the onset and progression of this unique keratopathy.

The use of sulfur hexafluoride microbubbles for contrast-enhanced ocular ultrasonography of the pecten oculi in birds

BACKGROUNDnThe pecten oculi is a vascular and pigmented structure localized within the posterior segment of all avian eyes. Its primary function is not fully understood yet.nnnOBJECTIVEnAs ultrasonography (US) is a useful imaging modality for evaluation of the pecten oculi, the objective of this study was to investigate the utility of an intravenous contrast solution of sulfur hexafluoride (SF6) microbubbles as a means of enhancing visualization of the pecten oculi in normal birds.nnnANIMALS STUDIEDnTen adult individuals of the following avian species were evaluated: 1 roadside hawk (Rupornis magnirostris), 1 stygian owl (Asio stygius), 2 striped owls (Asio clamator), 2 burrowing owls (Athene cunicularia), 2 ring-necked parakeet (Psittacula krameri), and 2 domestic chickens (Gallus gallus domesticus).nnnPROCEDURE(S)nAfter baseline ocular sonograms were obtained in sedated animals, 4.5xa0μg/kg of a contrast solution containing SF6 microbubbles was administered intravenously and US of the right eye was immediately performed. US was continued during injection to provide real-time imaging of the pecten oculi during vascular perfusion of contrast material.nnnRESULTSnWithin 2-3xa0seconds following intravenous contrast administration, microbubbles reached the pecten oculi of all birds investigated and provided significant ultrasonographic contrast enhancement.nnnCONCLUSIONSnSF6 microbubble contrast ultrasonography in birds is a safe and easy procedure that provides increased contrast and enhanced visualization of the pecten oculi. Future use may enable further discovery of its physiologic functions and aid in the development of therapeutic plans for avian intraocular disease.

A novel herpesvirus associated with chronic superficial keratitis and proliferative conjunctivitis in a great horned owl (Bubo virginianus)

An adult great-horned owl (Bubo virginianus; GHOW) presented with a history of recurrent corneal ulceration of the right eye (OD). Findings included ulcerative superficial keratitis, proliferative conjunctivitis, and iris pigmentary changes. The ulcer was initially nonresponsive to medical therapy, but showed rapid and appropriate healing following diamond burr debridement. Proliferative conjunctivitis markedly improved following topical antiviral therapy with cidofovir 1%, interferon alpha 2B ophthalmic solutions, and oral l-lysine. Histopathologic evaluation of a conjunctival biopsy revealed epithelial features suspicious for viral cytopathic changes and intranuclear structures suspicious for viral inclusions, suggestive of a possible viral-induced papillomatous conjunctivitis. A novel alphaherpesvirus, referred to as Strigid Herpesvirus 1 (StrHV1), was identified using PCR and gene sequencing. This case represents a new clinical manifestation of a previously unreported herpesvirus in the GHOW. Identification of the herpes virus was critical to administration of appropriate therapy and resolution of the conjunctivitis, and corneal epithelial debridement promoted resolution of the chronic corneal epithelial defect.

Presumed Photoreceptor Dysplasias In Peregrine Falcons (Falco peregrinus) and Peregrine Falcon Hybrids

Abstract: We describe a case series of photoreceptor dysplasia with secondary retinal degeneration in juvenile Peregrine Falcons. Six Peregrine Falcons (Falco peregrinus) and three Peregrine Falcon × Prairie Falcon (Falco mexicanus) hybrids had early-life visual deficits. Eight birds had visual defects shortly after hatching, and one bird had visual deficits first noticed at 5 mo of age. Complete ophthalmic examinations were performed in each animal. Eight of the animals had electroretinograms, and nine of the animals had their eyes examined histologically after euthanasia. Ophthalmic examinations did not reveal consistent and potentially blinding abnormalities, including an absence of ophthalmoscopic retinal lesions. Electroretinographic findings included subnormal amplitudes (with rod responses more abnormal than cone responses), with a negative b-wave amplitude occurring in one bird. Histologically, a reduction in the number of photoreceptors was present with numerous degenerative changes to the remaining photoreceptors, including frequent blunting and disorganization of photoreceptor outer segments, decreased numbers of cells in the inner nuclear layer, decreased numbers of ganglion cells, decreased thickness of the nerve fiber layer, and decreased myelinated axons within the optic nerve. Ultrastructurally, only minor cone outer segment changes and occasional phagocytic cells were seen. Results strongly suggested a primary retinopathy, characterized by photoreceptor dysplasia and secondary retinal degeneration with loss of cellular elements throughout the retina. The presence of a similar spectrum of findings in related individuals, the early age of onset, and the relative lack of other environmental, ocular, or systemic abnormalities suggested possible heritability.

A population study of common ocular abnormalities in C57BL/6N rd8 mice

Purpose The purpose of this study was to quantify the frequency and severity of ocular abnormalities affecting wild-type C57BL/6N mice, the most common strain used worldwide for the creation of single-gene knockouts. Methods A total of 2773 animals (5546 eyes) were examined at one colony at UC Davis and in three more colonies at the Institut Clinique de la Souris in Strasbourg, France. Mice were examined at 15 to 16 weeks postnatal age by performing anterior segment biomicroscopy, posterior segment examination by indirect ophthalmoscopy, intraocular pressure measurement, and optical coherence tomography of anterior and posterior segment structures. Results Common ocular findings in the C57BL/6N strain included corneal deposits (3%), increased optical density of the anterior lens capsule (67%), punctate nuclear cataracts (98%), vitreous crystalline deposits (61%), hyaloid vascular remnant (6%), and retinal dysplasia attributed to the rd8 mutation (58%). Interestingly, retinal dysplasia was more common in male mice in all four breeding colonies evaluated in this study. The thickness of ocular tissues and compartments were measured by spectral-domain optical coherence tomography, including the central cornea, anterior chamber, vitreous, and retinal layers. Intraocular pressure was measured by rebound tonometry. Conclusions Ocular abnormalities are common in anterior and posterior segments of the C57BL/6N mouse, the most common background on which single-gene knockout mice have been made. It is important that vision scientists understand the extent and variability of ocular findings associated with this particular genetic background of mice.

The Orientation of Visual Space from the Perspective of Hummingbirds

Vision is a key component of hummingbird behavior. Hummingbirds hover in front of flowers, guide their bills into them for foraging, and maneuver backwards to undock from them. Capturing insects is also an important foraging strategy for most hummingbirds. However, little is known about the visual sensory specializations hummingbirds use to guide these two foraging strategies. We characterized the hummingbird visual field configuration, degree of eye movement, and orientation of the centers of acute vision. Hummingbirds had a relatively narrow binocular field (~30°) that extended above and behind their heads. Their blind area was also relatively narrow (~23°), which increased their visual coverage (about 98% of their celestial hemisphere). Additionally, eye movement amplitude was relatively low (~9°), so their ability to converge or diverge their eyes was limited. We confirmed that hummingbirds have two centers of acute vision: a fovea centralis, projecting laterally, and an area temporalis, projecting more frontally. This retinal configuration is similar to other predatory species, which may allow hummingbirds to enhance their success at preying on insects. However, there is no evidence that their temporal area could visualize the bill tip or that eye movements could compensate for this constraint. Therefore, guidance of precise bill position during the process of docking occurs via indirect cues or directly with low visual acuity despite having a temporal center of acute vision. The large visual coverage may favor the detection of predators and competitors even while docking into a flower. Overall, hummingbird visual configuration does not seem specialized for flower docking.

THE EYE OF THE AZARA'S AGOUTI (DASYPROCTA AZARAE): MORPHOLOGICAL OBSERVATIONS AND SELECTED OPHTHALMIC DIAGNOSTIC TESTS

Abstract The purpose of this study was to carry out a descriptive investigation of the Azaras agouti (Dasyprocta azarae) eye and to establish reference values of select ophthalmic diagnostic tests and physiologic parameters. A total of 19 healthy agoutis were used. Select ophthalmic diagnostic tests were performed, including Schirmer tear test type I (STTI), analysis of the conjunctival bacterial microflora, corneal esthesiometry, and tonometry. B-mode ultrasonic biometry, fundus photography, optical coherence tomography, and gross and histologic analysis of two eyes were also performed. Reference range parameters found for the ocular diagnostic tests were esthesiometry, 4.50 ± 0.36 cm (0.7 ± 0.01 g/mm2); tonometry, 11.61 ± 0.44 mm Hg; palpebral fissure length, 1.70 ± 0.25 mm; STTI, 9.73 ± 0.47 mm/min; corneal thickness, 0.8 ± 0.003 mm; anterior chamber depth, 1.71 ± 0.07 mm; lens thickness, 5.03 ± 0.05 mm; vitreous chamber depth, 5.12 ± 0.01 mm; and globe axial length, 14.02 ± 0.01 mm. A paurangiotic, retinal, vascular pattern with a conspicuous pigment-laden optic disc was observed. The most frequent bacteria isolated were nonhemolytic Streptococcus sp. (36.84%), followed by Enterobacter harfinia (31.58%) and Escherichia coli (28.95%). No significant differences between genders or between left and right eyes were found for any of the results. Gross and histologic evaluation of two eyes confirmed the presence of melanocytic pigment granules between optic nerve fibers. The diagnostic values and the morphologic observations described here provide a reference to veterinarians to aid in the diagnosis of ocular disease.