Study on the ophthalmic diseases in ICR mice and BALB/c mice.

In pharmaceutical companies and research institutes, many toxicity tests are performed with laboratory animals. This study was performed to produce reference data for eye toxicity tests and to investigate the ophthalmic diseases of 408 ICR mice and 119 BALB/c mice, which are commonly used as subjects in toxicity tests. The experimental animals without clinical disorders were selected regardless of sex. The ophthalmic diseases were examined by using special ophthalmic instruments: direct ophthalmoscope, indirect ophthalmoscope, slit-lamp biomicroscope and focal illuminator. The most prevalent ocular variation within normal limits was hyaloid vessel remnant (ICR mice, 28.2%; BALB/c mice, 31.9%) and the incidence gradually decreased with age. The ocular diseases found in ICR mice were retinal degeneration (9.8%), corneal scar (4.2%), focal cataract (2.2%), anisocoria (1.2%), corneal ulcer (0.2%) and uveitis (0.2%). In BALB/c mice, corneal scar (9.2%), focal cataract (1.7%) and corneal ulcer (0.8%) were the ocular diseases found.     

Incidence of spontaneous ocular lesions in laboratory rabbits

Laboratory rabbits are commonly used for ocular drug and device studies. The purpose of this study was to determine the incidence of spontaneous ocular lesions in laboratory rabbits with respect to sex, breed, and supplier. We retrospectively evaluated ophthalmic examination records of rabbits screened between April 2008 and April 2010. These 1840 records represented 572 black Dutch belted (DB), 1022 New Zealand white (NZW), and 246 NZW × New Zealand red F(1) crosses (WRF1). Rabbits were between 6 and 16 wk of age and had been received from 5 suppliers. Ocular structures evaluated were the cornea, lens, iris and vitreous with respect to sex, breed and supplier. A total of 177 rabbits (9.6%) and 233 eyes (6.3%) were effected. Of total rabbits, 15.3% males and 7.3% females were affected. The most common structure affected was the cornea in 5.7% of rabbits, (DB 11.7%, NZW 3.0%, and NZR 3.3%). The lens at 3.6% was second most common (DB 2.1%, NZW 4.6%, and NZR 3.3%). Both iris (0.2%) and vitreous (0.3%) were not significantly affected. Significant sex-breeder-supplier combinations were: cornea DB supplier D, supplier D females, supplier D males, DB males and NZR females; and lens: NZW females; and at least one affected ocular structure: NZW supplier D, supplier D females, DB males, NZW females, and NZR females. Breed, sex, and supplier were significant variables of ocular lesions in laboratory rabbits. Investigators should consider each of these variables when choosing rabbits for ocular studies.     

Funduscopy in adult zebrafish and its application to isolate mutant strains with ocular defects

Funduscopy is one of the most commonly used diagnostic tools in the ophthalmic practice, allowing for a ready assessment of pathological changes in the retinal vasculature and the outer retina. This non-invasive technique has so far been rarely used in animal model for ophthalmic diseases, albeit its potential as a screening assay in genetic screens. The zebrafish (Danio rerio) is well suited for such genetic screens for ocular alterations. Therefore we developed funduscopy in adult zebrafish and employed it as a screening tool to find alterations in the anterior segment and the fundus of the eye of genetically modified adult animals.A stereomicroscope with coaxial reflected light illumination was used to obtain fundus color images of the zebrafish. In order to find lens and retinal alterations, a pilot screen of 299 families of the F3 generation of ENU-treated adult zebrafish was carried out.Images of the fundus of the eye and the anterior segment can be rapidly obtained and be used to identify alterations in genetically modified animals. A number of putative mutants with cataracts, defects in the cornea, eye pigmentation, ocular vessels and retina were identified. This easily implemented method can also be used to obtain fundus images from rodent retinas.In summary, we present funduscopy as a valuable tool to analyse ocular abnormalities in adult zebrafish and other small animal models. A proof of principle screen identified a number of putative mutants, making funduscopy based screens in zebrafish feasible.     

Effect of beta-adrenoblockers on prostaglandin-induced ocular hypertension in rabbits

It has been demonstrated in experiments on unanesthetized rabbits that propranolol instilled into the eye conjunctival sac caused a decrease in normal intraocular pressure and reduced prostaglandin-induced ocular hypertension. Thymolol and atenolol decreased the normal ophthalmic tone but did no affect eye hypertension. Oxprenolol and talinolol did not affect the normal ophthalmic tone and did not remove the elevation of intraocular pressure induced by PGE2.     

Anti-inflammatory, antioxidant and antimicrobial activity of Ophthacare brand, an herbal eye drops.

In the present study, the herbal preparation of Ophthacare brand eye drops was investigated for its anti-inflammatory, antioxidant and antimicrobial activity, using in vivo and in vitro experimental models. Ophthacare brand eye drops exhibited significant anti-inflammatory activity in turpentine liniment-induced ocular inflammation in rabbits. The preparation dose-dependently inhibited ferric chloride-induced lipid peroxidation in vitro and also showed significant antibacterial activity against Escherichia coli and Staphylococcus aureus and antifungal activity against Candida albicans. All these findings suggest that Ophthacare brand eye drops can be used in the treatment of various ophthalmic disorders.     

Ocular larva migrans caused by Toxocara cati in Mongolian gerbils and a comparison of ophthalmologic findings with those produced by T. canis

To elucidate the pathogenic potential of Toxocara cari, we observed the ophthalmologic changes of the fundi in Mongolian gerbils, Meriones unguiculatus, after oral inoculation of 17 embryonated eggs/g body weight. Ophthalmic conditions in 8 T. cati-infected gerbils were monitored using an ophthalmoscope from day 0 to day 156 and were compared with those of 57 T. canis-infected gerbils. The results showed that T. cati larvae migrated into the eye of the gerbil and then elicited ophthalmic changes, including retinal (25%) and vitreous (50%) hemorrhaging, vasculitis (37.5%), and exudative lesions (25%). Lesions were less prevalent, however, in T. cati-infected than in T. canis-infected gerbils. Unlike in T. canis-infected gerbils, the hemorrhagic lesions did not reappear in T. cati-infected gerbils after they were absorbed. These findings suggested that T. cati larvae are a potentially hazardous pathogen for ocular toxocariasis and that Mongolian gerbils infected with T. cati may be a useful model for the study of human ocular toxocariasis caused by T. cati. This is the first study to report that T. cati larvae can induce ophthalmic lesions in the retina of gerbils.     

Review of application of mass spectrometry for analyses of anterior eye proteome

Proteins have important functional roles in the body, which can be altered in disease states. The eye is a complex organ rich in proteins; in particular, the anterior eye is very sophisticated in function and is most commonly involved in ophthalmic diseases. Proteomics, the large scale study of proteins, has greatly impacted our knowledge and understanding of gene function in the post-genomic period. The most significant breakthrough in proteomics has been mass spectrometric identification of proteins, which extends analysis far beyond the mere display of proteins that classical techniques provide. Mass spectrometry functions as a "mass analyzer" which simplifies the identification and quantification of proteins extracted from biological tissue. Mass spectrometric analysis of the anterior eye proteome provides a differential display for protein comparison of normal and diseased tissue. In this article wepresent the key proteomic findings in the recent literature related to the cornea, aqueous humor, trabecular meshwork, iris, ciliary body and lens. Through this we identified unique proteins specific to diseases related to the anterior eye.     

Demand incidence and episode rates of ophthalmic disease in a defined urban population.

OBJECTIVES--To estimate demand incidence and episode rates of ophthalmic disease in a defined urban population over one year. DESIGN--Study of patients presenting with eye problems to general practice and eye casualty department. SETTING--General practice and ophthalmic services in west Nottingham. SUBJECTS--36,018 people from the combined practice lists of 17 Nottingham general practitioners. MAIN OUTCOME MEASURES--Ophthalmic disorder, age and sex of patient, and where presented. RESULTS--587 consultations were recorded for ophthalmic problems, 1771 with general practitioners and 816 with eye casualty. Most consultations to general practice were by females (1066 (60%)), whereas men aged 15-44 accounted for most work in eye casualty. These men commonly presented with trauma. Infective conjunctivitis, the commonest condition, had an episode rate of 13.5/1000 population/year. Demand incidence for cataracts was 1.9/1000 population/year. Demand incidence for chronic conditions increased with age. CONCLUSIONS--As the average age of the population increases demand for ophthalmic services will rise. Planning and provision of resources to meet this increased demand should be considered now.     

Pathogenicity of Pasteurella multocida A:3 in Flemish giant and New Zealand white rabbits.

Pasteurella multocida A:3 was isolated during an outbreak of pasteurellosis in Flemish Giant (FG) rabbits. Since New Zealand White (NZW) rabbits housed in the same room were not as severely affected as FG rabbits, experimental inoculation was undertaken to determine if FG rabbits were more susceptible than NZW rabbits to pasteurellosis induced by this isolate. Rabbits of each breed were inoculated with P. multocida A:3 and observed for 3 weeks. Four of 5 FG rabbits developed severe clinical disease on days 6, 9, 12 and 14 after inoculation; whereas, the one affected NZW rabbit became ill 14 days after inoculation. All rabbits with clinical disease developed fibrinosuppurative pleuritis, pyothorax and pneumonia which was more severe in FG than NZW rabbits. At necropsy, P. multocida A:3 was isolated from multiple sites of the diseased rabbits. No significant difference (P = 0.099) in the prevalence of lesions between the two breeds was found; however, the score of pneumonia and pleuritis was 3 times greater in FG rabbits than NZW rabbits.     

In vivo ocular availability of ketorolac following ocular instillations of aqueous,oil, and ointment formulations to normal corneas of rabbits: A technical note

Conclusions  In vivo ocular availability of ketorolac was evaluated following ocular instillation of aqueous, oil, and ointment formulations to normal corneas of rabbits and monitoring ketorolac concentration in aqueous humor by HPLC. Compared with aqueous drop, sesame and soybean oil drops of ketorolac provided higher ocular availability followed by ophthalmic ointment. The ointment formulation provided maximum sustained effect. Ketorolac aqueous drop with BAC and EDTA improved the rate of ocular absorption though not the extent. Published: October 24, 2005     

Congenital cataract in a cynomolgus monkey

The anterior part of the eye was examined with 1,531 newborn cynomolgus monkeys (Macaca fascicularis). A male (about 0.07%) of those newborns was noticed to have white opacities in his both eyes (Fig. 1). This finding was diagnosed to be bilateral congenital cataract by observing with a slit-lamp biomicroscope. Partial resorption of the white opaque part occurred one week after birth in the right eye (Fig. 2) and three weeks after birth in the left eye (Fig. 3). As a result of the resorption, observation of the ocular fundus by an ophthalmoscope became possible at two and seven weeks of age in the right and left eyes, respectively (Figs. 6 and 7), even though the ophthalmoscopic figures were not complete. White opacities occupied again nearly the whole area of the lens at 10 months of age in the left eye (Fig. 4) and at 14 months of age in the right eye (Fig. 5). Breeding studies are needed to determine if this case has any genetic background.     

Integrative analysis of ocular complications in atherosclerosis unveils pathway convergence and crosstalk

Abstract

Atherosclerosis is a life-threatening disease and a major cause of mortalities worldwide. While many of the atherosclerotic sequelae are reflected as microvascular effects in the eye, the molecular mechanisms of their development is not yet known. In this study, we employed a systems biology approach to unveil the most significant events and key molecular mediators of ophthalmic sequelae caused by atherosclerosis. Literature mining was used to identify the proteins involved in both atherosclerosis and ophthalmic diseases. A protein–protein interaction (PPI) network was prepared using the literature-mined seed nodes. Network topological analysis was carried out using Cytoscape, while network nodes were annotated using database for annotation, visualization and integrated discovery in order to identify the most enriched pathways and processes. Network analysis revealed that mitogen-activated protein kinase 1 (MAPK1) and protein kinase C occur with highest betweenness centrality, degree and closeness centrality, thus reflecting their functional importance to the network. Our analysis shows that atherosclerosis-associated ophthalmic complications are caused by the convergence of neurotrophin signaling pathways, multiple immune response pathways and focal adhesion pathway on the MAPK signaling pathway. The PPI network shares features with vasoregression, a process underlying multiple vascular eye diseases. Our study presents a first clear and composite picture of the components and crosstalk of the main pathways of atherosclerosis-induced ocular diseases. The hub bottleneck nodes highlight the presence of molecules important for mediating the ophthalmic complications of atherosclerosis and contain five established drug targets for future therapeutic modulation efforts.     

Venous stagnation induced by 7 dyas in HDT, in the cerebral, ophtalmic, renal and splancnhic territories

The scientific objectives was to quantify the vascular changes in the brain, eye fundus, renal parenchyma, and splanchnic network. Heart, Portal, Jugular, femoral veins were investigate by Echography. The cerebral mesenteric, renal and ophthalmic arteries were investigated by Doppler. Eye fundus vein an papilla were investigated by optical video eye fundus. The Left ventricle volume decreased as usual in HDT. The cerebral and ophthalmic vascular resistances did'nt change whereas the eye fundus papilla and vein, and the Jugular vein increased. These arterial and venous data confirm the existence of cephalic venous blood stasis without sign of intracranial hypertension. On the other hand the kidney volume increased which is in agreement with blood flow stagnation at this level. At last the Mesenteric vascular resistance decreased and the Portal vein section increased in HDT which is in favor of an increase in flow and flow volume through the splanchnic area.     

The natural histidine-containing dipeptide Nalpha-acetylcarnosine as an antioxidant for ophthalmic use

The naturally occurring compound Nalpha-acetylcarnosine is proposed as a prodrug of L-carnosine that is resistant to enzymatic hydrolysis by carnosinase. Eyes of rabbits were treated with 1% Nalpha-acetylcarnosine, L-carnosine, or placebo and extracts of the aqueous humor from the anterior eye chamber were analyzed for imidazole content by reverse-phase analytical high performance liquid chromatography (HPLC) and thin-layer (TLC) and ion-exchange chromatographic techniques. Topical administration of pure L-carnosine to the rabbit eye did not lead to accumulation of this compound in the aqueous humor over 30 min in concentration exceeding that in the placebo-treated matched eye. Nalpha-Acetylcarnosine showed dose-dependent hydrolysis in its passage from the cornea to the aqueous humor, releasing L-carnosine after l5-30 min of ocular administration of the prodrug in a series of therapeutic modalities: instillation < or = subconjunctival injection < or = ultrasound-induced phoresis. Different treatment techniques showed excellent toleration of 1%Nalpha-acetylcarnosine by the eye. Once in the aqueous humor, L-carnosine might act as an antioxidant and enter the lens tissue when present at effective concentrations (5-l5 mM). The advantage of the ophthalmic prodrug Nalpha-acetylcarnosine and its bioactivated principle L-carnosine as universal antioxidants relates to their ability to give efficient protection against oxidative stress both in the lipid phase of biological membranes and in aqueous environments. Nalpha-Acetylcarnosine is proposed for treatment of ocular disorders that have a component of oxidative stress in their genesis (cataracts, glaucoma, retinal degeneration, corneal disorders, ocular inflammation, complications of diabetes mellitus, and systemic diseases).     

Mechanisms of perioperative corneal abrasions: Alterations in the tear film proteome

Perioperative corneal abrasion is a common ophthalmic complication detectable in patients undergoing general anesthesia. In this study, using experimental perioperative corneal abrasion in animals (rabbits) correlations have been found between development of corneal abrasion and proteomic changes in the tear film. The process of accumulation of pathological changes in the cornea begins after 1 h of general anesthesia while after 3–6 h of general anesthesia clinically manifested abrasions have been recognized. The development of corneal abrasions was associated with different changes in the content of the major proteins of the tear film. Analysis of the tear proteome points to suppressed lachrymal gland functioning, and suggests that serotransferrin, serum albumin and annexin A1 may be applicable as potential tear markers of the ophthalmic complication. The biochemical changes in the tear film included the rapid decrease in total antioxidant activity and activity of superoxide dismutase, as well as the decrease in interleukin-4 and the increase in interleukin-6 content thus indicating development of oxidative and pro-inflammatory responses. These findings suggest that antioxidant and anti-inflammatory therapy is a prospective approach for prevention/treatment of perioperative corneal abrasions. The observed anesthesia-induced effects should be taken into consideration in any study of ocular surface diseases employing anesthetized animals.     

Aqueous, oil, and ointment formulations of ketorolac: efficacy against prostaglandin E2-induced ocular inflammation and safety: A technical note

The efficacy of aqueous, oil, and ointment formulations of ketorolac against PGE₂-induced ocular inflammation in rabbits was evaluated, with monitoring of blinking rate and PMN and protein migration in tear fluid, following topical PGE₂ instillation. Ketorolac ophthalmic formulations protected the eye against inflammatory insult. Chronic topical administration of formulations for 10 days into rats' eyes did not lead to any appreciable gastrointestinal ulceration, which indicates that the formulations are safe for long-term use.     

Referral patterns to an ophthalmic outpatient clinic by general practitioners and ophthalmic opticians and the role of these professionals in screening for ocular disease.

Case notes of 1113 consecutive new patients referred to a consultant ophthalmologist at a district general hospital were reviewed to determine the source and efficacy of referrals and the current screening practices of general practitioners and ophthalmic opticians. General practitioners initiated referral in 546 cases (49%) and ophthalmic opticians referral in 439 (39%). Visual loss or visual disturbance was the most important single reason for referral (345 cases; 31%), followed by suspected glaucoma (145 cases; 13%), abnormalities of binocular vision (140; 12.5%), disorders of eyelids or ocular adnexa (127; 11%), and red eye (86; 8%). General practitioners referred many more patients with disorders of the eyelids and adnexa and ophthalmic opticians many more patients with suspected glaucoma. Ophthalmic opticians were far more likely than general practitioners to refer patients with suspected glaucoma correctly. A total of 180 patients (16%) were referred from ocular screening, in 149 cases by ophthalmic opticians and in 10 by general practitioners. Seventy patients had glaucoma or incomplete features of glaucoma, all of them referred by ophthalmic opticians. Of eight diabetic patients referred by ophthalmic opticians, three had asymptomatic disease and in two diabetes was diagnosed as a result of ocular screening. No patient was referred for asymptomatic diabetic retinopathy from screening by general practitioners. Ophthalmic opticians were more likely than general practitioners to diagnose retinopathy requiring photocoagulation. Use of a community based service to screen for glaucoma could save unnecessary consultant outpatient appointments. A similar service could facilitate detection of diabetic retinopathy at a stage when treatment is most effective.     

The Fundus Oculi in Hypertension and Arteriosclerosis

Vascular and retinal changes seen with the ophthalmoscope in hypertension and arteriosclerosis are described, their pathogenesis is discussed, and the whole is integrated by means of a rational hypothesis.The morphological changes in the arterioles, in the venules, and at the arteriolarvenous crossings are considered, and a classification is suggested for ease of reference.Retinal changes (retinopathy) in these diseases and their pathogenesis are outlined, showing how their appearance may be used to assess the function of the peripheral vascular system and how they may reflect the general status.Because of the great variety of changes found in the fundus oculi, any adequate classification of the total fundus picture is not proposed. It is best to describe the findings objectively, and only then to speculate as to their significance.     

Effects of alloxan-induced diabetes on hemorheology in rabbits.

Plasma viscosity (PV), apparent whole blood viscosity (WBV), relative blood viscosity (RV) and erythrocyte deformability (filterability) (EDF) were determined in 13 New Zealand White (NZW) rabbits with alloxan induced-diabetes (AID) and 8 normal NZW rabbits, matched for age, sex and weight. AID rabbits were divided into two groups depending on the duration of hyperglycemia (long-term, greater than 6.0 months (n = 7), and short-term, less than or equal to 3.0 months of hyperglycemia, n = 6). Comparing long-term AID rabbits to normal animals, we found significant increases in WBV (P less than 0.001, 0.005 for high and low rates of shear, respectively), and a marked reduction in EDF (P less than 0.001). There was no significant difference in PV between long-term AID and normal rabbits. Conversely, PV was significantly increased in rabbits with short-term diabetes (P less than 0.01) while there was a concurrent significant increase in WBV measured at high and low rates of shear (P less than 0.001, 0.001, respectively). No difference was detected in EDF between normal and short-term AID rabbits. Furthermore, in long-term AID rabbits there was a strongly positive correlation between RV and reduced erythrocyte deformability (r = 0.94, P = 0.006) while WBV strongly correlated with PV (r = 0.92, P = 0.004) in the short-term AID subgroup. We conclude from these data: (1) elevated blood viscosity in long term AID rabbits is associated with reduced erythrocyte filterability; and (2) elevated WBV in short-term AID rabbits is associated with increased PV.     

Congenital entropion in a litter of rabbits

Conjunctivitis and blepharospasm were observed in a litter of four, 2-week-old New Zealand white rabbits. Corneal opacity and neovascularization of the cornea and entropion of the upper eyelids were observed when the rabbits were examined 10 weeks later. Conjunctival cultures of these rabbits yielded normal bacterial flora. Treatment with a steroid-antibiotic ophthalmic ointment did not alter the ocular abnormalities. Surgical correction of the entropion resulted in a complete regression of all clinical signs.