Persistent fetal intraocular vasculature in the European ferret (Mustela putorius): clinical and histological aspects

Objective To describe the clinical and histological appearance of persistent fetal intraocular vasculature in a colony of ferrets.
Design Prospective study.
Animals studied Eighty-six European ferrets ( Mustela putorius ).
Procedure Both eyes of 76 genetically related progeny and 10 breeding, adult, colony-raised ferrets were studied using a slit lamp biomicroscope and an indirect ophthalmoscope. Ferret progeny were examined after eyelid opening at 5–6 weeks of age, and at 12 months of age. After euthanasia, globes were enucleated and examined histologically.
Results Persistent fetal intraocular vasculature was evident in 21 progeny ferrets at 5–6 weeks of age and in three mature progenitor ferrets. Clinical appearance of diminutive vasculature was characterized by focal remnants of the posterior tunica vasculosa lentis, muscae volitantes, and an occluded hyaloid artery extending from the optic papilla and terminating in the anterior vitreous body. Extensive persistent vasculature was characterized by a perfused hyaloid artery, vasa hyaloidea propria and posterior tunica vasculosa lentis, posterior cortical and capsular cataract, and proliferation of fibrovascular tissue along the posterior lens capsule. Fetal vasculature persisted in 7 of 21 progeny ferrets at one year of age and in three progenitor ferrets. Results of histologic examination showed persistence of the hyaloid vasculature, proliferation of retrolental fibrovascular tissue with osseous metaplasia, posterior capsular and cortical cataract, and occasional retinal detachment.
Conclusions Persistent fetal intraocular vasculature in ferrets appears similar clinically and histologically to persistent fetal intraocular vasculature reported in humans and dogs. The ferret may be a suitable animal model for vasculogenic mechanisms of persistent fetal intraocular vasculature and for evaluating vasoinhibitory growth factors and angiostatic test compounds.     

Persistent hyperplastic tunica vasculosa lentis and persistent hyaloid artery in a 2-year-old basset hound.

A 2-year-old Basset hound with unilateral persistent hyperplastic tunica vasculosa lentis and primary vitreous is described. There was leukokoria in the left eye, caused by bluish-white polar densities and haemorrhagic discoloration in the nucleus of the lens. Ultrasonographic examination of the eye revealed a small hyperechoic lens and a hyperechoic linear soft-tissue strand extending from the posterior pole of the lens through the optic disc. Power Doppler imaging revealed blood flow in this persistent hyaloid artery, but 5 months later, immediately prior to surgery, there was no flow in this artery. Ultrasonography, including Power Doppler imaging, was useful to confirm the diagnosis and to estimate the complications of surgery, especially the risk of vitreal haemorrhage after cutting of the persistent hyaloid artery. Comparison of the ultrasonographic images with those obtained by computed tomography suggested that the resolution of computed tomography is inadequate for identifying structures as fine as a persistent hyaloid artery.     

Experimental determination and allometric prediction of vitreous volume, and retina and lens weights in Göttingen minipigs

Objectives To determine the vitreous volume, and retinal and lens wet weights in male and female Göttingen minipigs of different age groups. Procedures Vitreous, lens and retina were isolated from fresh minipig eyes. Vitreous volume, lens and retina weight were measured and allometric scaling was utilized to predict these parameters. Results There were no gender differences in body weights or retina and lens weights in the three age groups examined in this study. For vitreous volumes, females had a significantly larger volume (approximately 10%–12%) than males in the 4–6 and 6–8 month, but not in the 8–11‐month group. The mean body weight increased from 12.2 ± 2.6 kg (4–6 months) to 19.4 ± 4.0 kg (8–11 months). In the same period, the mean vitreous volume increased from 2.00 ± 0.28 to 2.67 ± 0.31 mL, while the mean retinal and lens weights increased from 114 ± 22 to 126 ± 17 mg, and from 298 ± 26 to 392 ± 15 mg, respectively. Allometric analysis between six species for vitreous volume and four species for lens weight covering a weight range of 260‐fold was not able to estimate the vitreous volume, but it did predict the lens weight in 8–11 months minipigs. Conclusions Overall these measurements add important context to intraocular pharmacology studies, and will help in the improved design and interpretation of such experiments.     

ULTRASONOGRAPHIC EVALUATION OF PRE- AND POSTNATAL DEVELOPMENT OF THE EYES IN BEAGLES

Transabdominal ultrasonography was performed to visualize the development of intraocular structures of both eyes of four different fetuses in each of two pregnant beagles. Postnatally the development of both eyes of 11 pups was visualized with ultrasonography. Furthermore, biometric measurements of the length of the eye, the depth of cornea, the anterior chamber, the lens (anteroposterior depth and equatorial diameter), and the vitreous body of the fetuses and pups were obtained when these structures could be identified with ultrasonography. In all fetuses the eyes with lens, vitreous body, hyaloid artery, and scleroretinal rim could be clearly identified from day 37 of pregnancy. Postnatally also the cornea, anterior chamber, iris, ciliary body, and optic disc were visible. Biometric measurements revealed, both pre- and postnatally, a continuous growth of the depth of the eye, anterior chamber, lens (anteroposterior depth and equatorial diameter), and vitreous body.     

Hyaloid artery patency in neonatal beagles

The patency of the hyaloid artery in neonatal Beagles was evaluated after liquid latex perfusion. As early as postpartum day 5, some pups had closure of the most distal branches of the vessels of the posterior lens tunica, but in these, many larger branches were open. Other pups at postpartum days 5 and 6 had substantially all of the blood vessels of the posterior tunica vasculosa lentis open. Few tunica vessels were patent in any pups beyond day 13, and none was patent after day 17. Persistent hyaloid remnants at the optic disk were evident in 3 of 16 pups 17 to 28 days old, but absent in the others.     

Ocular complications of persistent hyperplastic primary vitreous in three dogs

Persistent hyperplastic primary vitreous (PHPV) syndrome associated with either severe ocular complications or multiple ocular lesions was diagnosed in three young dogs, a Samoyed, a Spanish Pachon, and a mixed breed dog. Due to opacification of the anterior ocular structures, B-mode and color-flow Doppler ultrasonography were performed to aid diagnosis. The Samoyed presented with unilateral hyphema; the Spanish Pachon presented with unilateral secondary glaucoma associated with uveitis and hyphema OD and leucocoria OU; and the mixed breed presented with bilateral leucocoria. B-mode ultrasonography of the Samoyed revealed a subcapsular cataract and a hyperechoic tubular structure attached from the optic disk to the posterior lens capsule. In the Spanish Pachon B-mode ultrasonography of the right eye indicated microphakia, cataract formation, and a retrolental mass with a thin hyperechoic strand stretching from the optic disk to the posterior lens; and for the right eye cataract formation, PHPV, retinal detachment, and vitreous hemorrhage. In the mixed breed dog, B-mode ultrasonography of both eyes indicated microphthalmia, retrolental mass, and hyperechoic lenses. By color-flow Doppler imaging, blood flow was present in the retrolental mass of the right eye suggesting a persistent hyaloid artery.     

Spontaneous ophthalmic lesions in young Sprague-Dawley rats.

Eight hundred eight Sprague-Dawley rats were examined for ophthalmic abnormalities during a pretest period in various preclinical safety assessment studies. Persistent pupillary membrane, corneal crystal, healed minor trauma, synechia, coloboma of the iris, lens luxation, cataract, persistent hyperplastic primary vitreous, vitreous hemorrhage, coloboma of the optic disc or choroid, remnant of hyaloid arterial system, retinal hemorrhage, retinal detachment, retinal folding and choroidal defect were observed. The incidences of corneal crystal, synechia, and nuclear cataract in this survey were higher than those reported previously. On the other hand, retinal folding in this survey was less common than that reported previously. These results suggest that background data of eye problems in albino rats should be accumulated in each own laboratory colony. In addition, since spontaneous eye problems are common in young albino rats, elimination of rats with ophthalmic abnormalities from study groups by an ophthalmic examination during a pretest period would facilitate to evaluate toxicity potential of test compounds in safety assessment studies.     

Congenital multiple ocular defects with falciform retinal folds among Japanese black cattle

To clarify the morphologic features of the ocular disease recently occurring among Japanese Black cattle in southern Kyushu, 6 globes from 3 Japanese Black cattle, between 11 and 20 months old (cow Nos. 1 to 3), were pathologically examined. Cow Nos. 1 and 2 were sired by the same Japanese Black bull, and cow No. 3 was sired by the ancestor (sire) of the former bull. The ocular lesions were pathologically similar to each other, except for the left eye of cow No. 1. The ocular lesions of 5 globes were characterized by microphthalmia, hypoplasia, and/or dysplasia of the lenses; persistence of the primary vitreous; and retinal dysplasia with total nonattachment. The left globe from cow No. 1 had no lens and severe hypoplasia and nonattachment of the retina. Because dysplastic retinal lesions that formed crescentic folds and a central column were the most characteristic features of the eyes, the falciform retinal fold with congenital nonattachment was the most likely disease entity. Although the cause of the ocular disease could not be clarified with the present study, an inherited ocular defect of the bull and its ancestor was suspected.     

Ultrasonographic anatomy of the bovine eye.

The purposes of the study were to describe the ultrasonographic appearance and measurements of the normal bovine eye, to compare the measurements to those reported previously for cadaveric eyes and to describe differences between ocular dimensions of Holstein Friesian and Jersey cattle. Sixty transpalpebral ocular ultrasonographic examinations were performed on 30 adult Holstein Friesian cows, and 16 examinations were performed on 8 adult Jersey cows. Transpalpebral ultrasonographic images were obtained with a 10 MHz linear transducer in both horizontal and vertical imaging planes. The ultrasonographic appearance of structures within the bovine eye is similar to that in other species, although the ciliary artery was frequently identified, appearing as a 0.33 +/- 0.04 cm diameter hypoechoic area. The axial length of the globe was significantly greater in Holstein Friesian cattle (3.46 +/- 0.09 cm) compared with Jersey cattle (3.27 +/- 0.19 cm; P = 0.001), although the vitreous depth was smaller in Holstein Friesian cattle (1.46 +/- 0.09 cm) (P = 0.0009). The anterioposterior depth of the lens was significantly greater in Jersey cattle (1.92 +/- 0.11 cm) and the cornea was thinner in Jersey cattle (0.17 +/- 0.02 cm). The appearance and ocular distances for live animals were similar to those reported previously for cadaveric specimens. The knowledge of normal ocular dimensions facilitates the use of ultrasonography in the evaluation of ocular disease in cattle.     

Congenital ocular anomalies and ventricular septal defect in a dromedary camel (Camelus dromedarius).

A 5-wk-old female dromedary camel (Camelus dromedarius) was clinically diagnosed with bilateral corneal dermoids, incomplete congenital cataracts, a left persistent hyaloid artery (PHA), and a ventricular septal defect (VSD). The corneal dermoids were removed by lamellar keratectomy, and vision improved in the left eye. Thirteen months after dermoid surgery, the calf was presented for enlargement of the right eye. Glaucoma was confirmed in the right eye, and corneal fibrosis and cataract were noted in the left eye. Persistence of the VSD was confirmed by cardiac ultrasonography. The calf was euthanized, and necropsy findings confirmed VSD. Histopathologic examination revealed bilateral corneal thinning and fibrosis, cataracts with retrolental fibroplasia, and retinal dysplasia. Additional changes in the right globe were anterior segment dysgenesis, ruptured lens capsule, chronic phacoclastic uveitis, and retinal separation. The PHA was confirmed in the left eye.     

ULTRASONOGRAPHIC DIAGNOSIS OF PERSISTENT HYPERPLASTIC TUNICA VASCULOSA LENTIS/PERSISTENT HYPERPLASTIC PRIMARY VITREOUS IN TWO DOGS

Ultrasonography was performed on a Basset hound and a Doberman clinically suspected of persistent hyperplastic tunica vasculosa lentis/persistent hyperplastic primary vitreous. In both dogs, hyperechoic lenses with a triangular-shaped echodense structure retrolentally were visible, and a very thin hyperechoic strand was seen penetrating the anechoic vitreous from this retrolental tissue to the area of the optic nerve. Using color Doppler imaging, blood flow was evident in parts of the retina in both dogs. With power Doppler imaging there was blood flow in the lens and hyperechoic strand of the Basset hound on the first examination; whereas, on re-examination 5 months later, this was not found. Other abnormalities, such as retinal detachment, endophthalmitis, vitreous hemorrhage, microphthalmia, and posterior neoplasia could be excluded.     

Age changes in the eyes of the Beagle dog

Changes with age in the eyes of Beagle dogs are described clinically and histologically. Lenticular changes involve increased prominence of the posterior lens sutures and opacity within the fetal nucleus. Cystoid degeneration of the retina was found in 85% of 8–year–old animals examined. A pigmentary change of the retina was found to be associated with focal degenerative change of the tapetum. No case of retinal atrophy was recorded.     

Inheritance of associated ocular and skeletal dysplasia in Labrador retrievers

A breeding colony was established to investigate the inheritance of associated ocular and skeletal dysplasia in Labrador Retrievers; 124 pups were produced. These pups were evaluated for the presence of ocular lesions, including cataracts, vitreous strands, persistent hyaloid remnants, retinal folds, retinal dysplasia, peripapillary hyperreflectivity, and rhegmatogenous retinal detachments, and skeletal abnormality, which was recognized by shorter than normal forelimbs and an abnormal morphologic appearance of the radius and ulna. Analysis of the distribution of lesions in pups indicated that the syndrome is caused by one abnormal gene, which has recessive effects on the skeleton and incompletely dominant effects on the eye. This would suggest that suspect carrier dogs could be identified by test matings with a known homozygote.     

ULTRASONOGRAPHIC AND BIOMETRIC EVALUATION OF SHEEP AND CATTLE EYES

The normal ultrasonographic anatomy and biometry of 60 adult sheep and 60 adult cattle eyes were evaluated by saline immersion technique. Five intraocular dimensions were taken: corneal thickness, aqueous chamber depth, lens diameter, vitreous chamber depth and axis bulbi. The eyes were then frozen and cut in a sagittal plane and the same dimensions were measured directly. A- and B-mode measurements were compared with each other and with that of direct measurements. There was no difference between A- and B-mode measurements. However, there was a difference between ultrasound and direct measurements.     

Distribution and elimination of clenbuterol in tissues and fluids of calves following prolonged oral administration at a growth-promoting dose

A pharmacokinetic study is described in which Friesian calves (n = 30) were treated orally with clenbuterol at 10 times the therapeutic dose. The study was designed to establish the distribution and elimination of clenbuterol from edible tissues, the major compartments of the eye and body fluids. Animals (n= 24) were dosed (10 μg/kg body weight) twice daily with clenbuterol for 21 days and slaughtered in groups of five (one untreated control animal per group) at 6 h and 1, 2, 4, 8 and 16 days after cessation of treatment At slaughter, samples of diaphragm muscle, liver, kidney, bile, urine and both eyes were obtained. One of the eyes was separated into constituent tissues: aqueous humour, vitreous humour, comea, lens, retina (without pigmented epithelium), choroid (with pigmented retinal epithelium; choroid/PRE) and sclera. All samples were stored at -20°C. Clenbuterol concentrations were higher in liver than kidney, bile and urine from day 2 of withdrawal onwards. Concentrations in choroid/PRE were at least 10 times higher than in liver at all periods following cessation of treatment and 52 times higher 16 days after treatment The concentrations of clenbuterol in the constituent tissues of the eye were in the order choroid/PRE > comea > sclera > retina > aqueous humour/vitreous humour ≥ lens. Concentrations of clenbuterol in choroid/PRE taken from eyes frozen whole were generally lower than those in choroid/PRE separated before storage. Choroid/PRE stored by either method contained clenbuterol at more than 100 ng/g 16 days following cessation of treatment These data suggest that analysis of choroid taken at the abattoir would provide reliable surveillance information on the use or abuse of clenbuterol within the slaughter population. It is proposed that liver samples taken concurrently could be used in the event of a positive result from choroid/PRE analysis to indicate whether the maximum residue limit for edible tissues has been exceeded.     

Intraocular melanoma in a horse.

Sudden unilateral blindness occurred in a 7-year-old grey gelding Quarterhorse. Ophthalmoscopy revealed a pigmented mass arising from the nasal ciliary body of the right eye and extending around the posterior surface of the lens, and there were pigmented particles in the vitreous. Examination of the enucleated globe showed a circumscribed, black, dense and symmetrically ovoid mass with sessile attachment to the nasal ciliary region and extension to posterior lens capsule, vitreous and along the vitreal face of the detached retina to the optic papilla. The mass was composed of heavily pigmented, plump, polyhedral cells that invaded the vitreous and the inner limiting membrane of peripapillary retina and optic papilla. It was considered to be a primary, malignant, intraocular melanoma arising from a large uveal nevus.     

Inherited eye disease in the dog and cat

This paper describes the more common inherited eye conditions in the dog and cat, paying particular attention to the newer conditions, not all of which have previously been reported in the literature. These newer conditions include entropion in the shar pei, microphthalmos in the dobermann and miniature schnauzer, cataract in the German shepherd dog and Norwegian buhund, progressive retinal atrophy in the Tibetan terrier, Tibetan spaniel, miniature longhaired dachshund and two forms in the Abyssinian cat, multifocal retinal dysplasia in the English springer spaniel and other breeds, persistent hyperplastic primary vitreous in the Staffordshire bull terrier and dobermann and optic nerve hypoplasia in the toy poodle. Anatomical classification presents a convenient means of describing these conditions which may affect the whole globe, the eyelids, the nictitating membrane, the nasolacrimal duct system, the conjunctiva, the cornea, the aqueous, the iris, the lens and zonule, the vitreous, the retina, the choroid and sclera and the optic nerve.     

Functional and structural assessment of retinal sheet allograft transplantation in feline hereditary retinal degeneration

Purpose  To investigate whether sheets of fetal retinal allografts can integrate into the dystrophic Abyssinian cat retina with progressive rod cone degeneration.
Methods  Fetal retinal sheets (cat gestational day 42), incubated with BDNF microspheres, were transplanted to the subretinal space of four cats at an early disease stage. Cats were studied by fundus examinations, bilateral full-field flash ERGs, and indocyanine green and fluorescein angiograms up to 4 months following surgery. E42 donor and transplanted eyes were analyzed by histology and immunohistochemistry for retinal markers.
Results  Funduscopy and angiography showed good integration of the transplants in two of four cats, including extension of host blood vessels into the transplant and some scarring in the host. In these two, transplants were found in the subretinal space with laminated areas, with photoreceptor outer segments in normal contacts with the host retinal pigment epithelium. In some areas, transplants appeared to be well-integrated within the host neural retina. Neither of these two cats showed functional improvement in ERGs. In the other two cats, only remnants of donor tissue were left. Transplants stained for all investigated cellular markers. No PKC immunoreactivity was detected in the fetal donor retina at E42, but developed in the 4-month-old grafts.
Conclusions  Fetal sheet transplants can integrate well within a degenerating cat retina and develop good lamination of photoreceptors. Functional improvement was not demonstrated by ERG in cats with well-laminated grafts. Transplants need to be further evaluated in cat host retinas with a more advanced retinal degeneration using longer follow-up times.     

Expression of small leucine-rich proteoglycans in the developing retina and kainic acid-induced retinopathy in ICR mice

The aim of this study was to determine the developmental changes of small leucine-rich proteoglycans (PGs), decorin, biglycan and fibromodulin, in ICR mouse retinas and to elucidate their role in the adult retina using kainic acid (KA)-induced retinal degeneration model. Retinas of prenatal, postnatal and adult mice were collected for histological and immunohistochemical staining to investigate the changes in distribution of these PGs. Decorin-and fibromodulin-immunostainings were diffusely distributed at prenatal and early postnatal stages and were stronger in the adult retina. However, biglycan was moderately distributed in the prenatal and early postnatal stages and was faint in the adult retina. Retinas were collected at 1, 3 and 7 days after intravitreal injection of KA. Retinas of KA injected eyes underwent shrinkage accompanied by serious damage in the inner layers. Decorin and fibromodulin were upregulated in the inner retinal layers of KA-injected eyes compared to the normal ones. Our results suggest that decorin and fibromodulin play key roles in retinal differentiation, and contribute to the retinal damage and repair process. However, biglycan may have no or only a limited role in the mouse retinal development or repair process.     

Changes in the distribution of labeled retinal ganglion cells after an implant of DiI into the optic nerve in the chick embryos

Changes in the distribution of retinal ganglion cells (RGCs) were studied using the retrograde labeling of DiI in chicks and chick embryos. The small retinal area filled with labeled RGCs was observed in the retinal fundus on E8. The labeled retinal area expanded radially toward the peripheral retina as the retina grew, and finally occupied a whole retina by P1. The temporal retina was labeled more rapidly than in the nasal retina. The observed-increasing rate of the labeled area was corrected with the growing rate of the retina. Consequently, the corrected-increasing rate of the labeled area was estimated to be about 390% between E8 and E11, and 20-50% after E11. This means that spreading speed of the maturated RGCs lowered until 1/10-1/20 after E11.