Biomedical subjects

David L Williams

Publications and source records attributed to David L Williams.

At least 109 records · Page 6Linked to original sources

PubMed2002

Dectin-1 is a major beta-glucan receptor on macrophages.

Zymosan is a beta-glucan- and mannan-rich particle that is widely used as a cellular activator for examining the numerous responses effected by phagocytes. The macrophage mannose receptor (MR) and complement receptor 3 (CR3) have historically been considered the major macrophage lectins involved in the nonopsonic recognition of these yeast-derived particles. Using specific carbohydrate inhibitors, we show that a beta-glucan receptor, but not the MR, is a predominant receptor involved in this process. Furthermore, nonopsonic zymosan binding was unaffected by genetic CD11b deficiency or a blocking monoclonal antibody (mAb) against CR3, demonstrating that CR3 was not the beta-glucan receptor mediating this activity. To address the role of the recently described beta-glucan receptor, Dectin-1, we generated a novel anti-Dectin-1 mAb, 2A11. Using this mAb, we show here that Dectin-1 was almost exclusively responsible for the beta-glucan-dependent, nonopsonic recognition of zymosan by primary macro-phages. These findings define Dectin-1 as the leukocyte beta-glucan receptor, first described over 50 years ago, and resolves the long-standing controversy regarding the identity of this important molecule. Furthermore, these results identify Dectin-1 as a new target for examining the immunomodulatory properties of beta-glucans for therapeutic drug design.

Animals↗

PubMed2002

Apolipoprotein A-I is necessary for the in vivo formation of high density lipoprotein competent for scavenger receptor BI-mediated cholesteryl ester-selective uptake.

The severe depletion of cholesteryl ester (CE) in steroidogenic cells of apoA-I(-/-) mice suggests that apolipoprotein (apo) A-I plays a specific role in the high density lipoprotein (HDL) CE-selective uptake process mediated by scavenger receptor BI (SR-BI) in vivo. The nature of this role, however, is unclear because a variety of apolipoproteins bind to SR-BI expressed in transfected cells. In this study the role of apoA-I in SR-BI-mediated HDL CE-selective uptake was tested via analyses of the biochemical properties of apoA-I(-/-) HDL and its interaction with SR-BI on adrenocortical cells, hepatoma cells, and cells expressing a transfected SR-BI. apoA-I(-/-) HDL are large heterogeneous particles with a core consisting predominantly of CE and a surface enriched in phospholipid, free cholesterol, apoA-II, and apoE. Functional analysis showed apoA-I(-/-) HDL to bind to SR-BI with the same or higher affinity as compared with apoA-I(+/+) HDL, but apoA-I(-/-) HDL showed a 2-3-fold decrease in the V(max) for CE transfer from the HDL particle to adrenal cells. These results indicate that the absence of apoA-I results in HDL particles with a reduced capacity for SR-BI-mediated CE-selective uptake. The reduced V(max) illustrates that HDL properties necessary for binding to SR-BI are distinct from those properties necessary for the transfer of HDL CE from the core of the HDL particle to the plasma membrane. The reduced V(max) for HDL CE-selective uptake likely contributes to the severe reduction in CE accumulation in steroidogenic cells of apoA-I(-/-) mice.

Animals↗

PubMed2002

The disulfide redox system of Schistosoma mansoni and the importance of a multifunctional enzyme, thioredoxin glutathione reductase.

Schistosoma mansoni, a causative agent of schistosomiasis, is a major cause of human morbidity in tropical countries. Adult schistosomes, which reside in the hepatic portal system, are exposed to reactive oxygen compounds through respiration and as a result of the host immune response. To minimize oxidative stress schistosomes must possess adequate mechanisms of detoxification. Major detoxification systems rely on reducing equivalents from the disulfide oxidoreductases glutathione and thioredoxin. Therefore, maintenance of adequate levels of these thiols in a reduced form is critical. Here we show that S. mansoni possess an unusual thiol redox system centered on thioredoxin glutathione reductase. This enzyme represents an unusual fusion of a pyridine nucleotide disulfide oxidoreductase with a redox active glutaredoxin extension. Furthermore, we predict that this is a selenocysteine protein. Immunoprecipitation, western blot and inhibitor studies show that this protein has thioredoxin reductase, glutathione reductase, and glutaredoxin activities. Most importantly, we show that thioredoxin glutathione reductase appears to be the major, if not the sole enzyme for these activities in adult worms, completely replacing thioredoxin reductase and glutathione reductase. This is the first example of an organism with a redox system based exclusively on thioredoxin glutathione reductase.

Amino Acid Sequence↗

PubMed2002

Molecular and enzymatic characterisation of Schistosoma mansoni thioredoxin.

Defense against oxidative damage can be mediated through glutathione and/or thioredoxin utilising systems. Here, we report the identification and characterisation of a thioredoxin from Schistosoma mansoni. The predicted protein has similarity to previously characterised thioredoxins including conservation of the redox active site. Recombinant six-histidine tagged schistosome thioredoxin had insulin reduction activity and supported the enzymatic function of thioredoxin reductase and thioredoxin peroxidase. By Western blotting, all mammalian stages of the schistosome lifecycle expresses thioredoxin. Thioredoxin is present in egg secretory products and antibodies against the recombinant protein produce the circumoval precipitin reaction. This is the first identification of defined antigen producing this reaction. Furthermore, thioredoxin is a novel egg immunogen as it elicits an antibody response in schistosome-infected mice. The most significant IgG production against thioredoxin occurs after parasite oviposition commences. These observations suggest that thioredoxin participates in processes vital to the parasite and may facilitate the passage and survival of eggs across inflamed host tissues.

Amino Acid Sequence↗

PubMed2002

Adenylosuccinate lyase of Schistosoma mansoni: gene structure, mRNA expression, and analysis of the predicted peptide structure of a potential chemotherapeutic target.

Adenylosuccinate lyase is an enzyme used in parasite nucleotide salvage pathways that cleaves adenylosuccinate into adenosine 5'-monophosphate and fumarate. A cDNA encoding adenylosuccinate lyase from the trematode parasite Schistosoma mansoni has been cloned for analysis. Sequencing of the cDNA revealed an open reading frame of 1454 nucleotides that codes for a protein with a predicted mass of about 54.5 kDa. Comparative analysis of the predicted protein sequence shows that S. mansoni adenylosuccinate lyase has a lot of similarity with human adenylosuccinate lyase. Genomic analysis using S. mansoni adenylosuccinate lyase-containing bacterial artificial chromosome (BAC) clones revealed a gene of approximately 19.4 kb consisting of eight exons and seven introns. Intron 6 was found to contain a novel 2.9 kb long terminal repeat retrotransposon with direct terminal repeats of 500 nucleotides. Fluorescence in situ hybridisation mapping localised S. mansoni adenylosuccinate lyase to the Z and W chromosomes. Analysis of S. mansoni adenylosuccinate lyase mRNA expression levels using real time reverse transcriptase (RT)-PCR showed that S. mansoni adenylosuccinate lyase is expressed at higher levels in the female worms than in the male worms and is expressed at different levels than other purine nucleotide salvage enzymes. Male homogenate showed a specific activity of 10.3 units/mg protein while the female showed a specific activity of 24.2 units/mg protein. These data indicate that S. mansoni adenylosuccinate lyase is an important parasite enzyme and should be examined as a potential chemotherapeutic target.

Adenylosuccinate Lyase↗

PubMed2002

Risk factors for early cytologic abnormalities after loop electrosurgical excision procedure.

OBJECTIVE: To evaluate risk factors for early cytologic abnormalities and recurrent cervical dysplasia after loop electrosurgical excision procedure (LEEP). METHODS: A retrospective analysis was performed of all pathology records for LEEPs performed at our institution from January 1996 through July 1998. Follow-up cytology from 2 through 12 months after LEEP was reviewed. Patients with abnormal cytology were referred for further colposcopic evaluation. Statistical analysis using chi2 test for trend, proportional hazards model test, Fisher exact tests, and life table analysis were performed to identify risk factors for early cytologic abnormalities after LEEP and to determine relative risk of recurrent dysplasia. RESULTS: A total of 298 women underwent LEEP during the study period, and 29% of these had cytologic abnormalities after LEEP. Grade of dysplasia, ectocervical marginal status, endocervical marginal status, and glandular involvement with dysplasia were not found to be independent risk factors for early cytologic abnormalities. However, when risk factors were analyzed cumulatively, the abnormal cytology rate increased from 24% with no risk factors to 67% with three risk factors present (P =.037). Of patients with abnormal cytology after LEEP, 40% developed subsequent dysplasia, and the mean time to diagnosis was approximately 6 months. The relative risk of subsequent dysplasia ranged from a 20% increase to twice the risk if post-LEEP cytology was low-grade squamous intraepithelial lesion or high-grade squamous intraepithelial lesion, respectively. CONCLUSION: Based on these results, consideration should be given for early colposcopic examination of patients who have evidence of marginal involvement or endocervical glandular involvement with dysplasia. These patients are at increased risk for abnormal cytology and recurrent dysplasia. This initial visit should occur at 6 months, as the mean time to recurrence of dysplasia was 6.5 months.

Carcinoma, Squamous Cell↗

PubMed2002

Biology and pathology of the invertebrate eye.

Although this article is not a comprehensive review of ocular biology and disease across the millions of invertebrate species, it is hoped that it highlights the surprising gene homologies that influence ocular development despite the dramatic differences in resulting ocular development and final morphology. In the same way that ocular anatomy and physiology is undergirded by similarities in the genetic foundation of the eye, it is to be expected that eye disease in invertebrates, as it is studied in more depth, will show substantial homologies with the eye disease of the vertebrates that veterinary ophthalmologists are more used to treating.

Animals↗

PubMed2002

Ocular disease in rats: a review.

The rat Rattus norvegicus is widely used in experimental work, both providing a rodent model for human ocular disease and as a species for toxicologic screening. In addition, the rat is more and more widely kept as a pet, being both friendly and intelligent. Diagnosis and treatment of ocular disease is important for the welfare of individual animals and whole colonies, but also to ensure that spontaneous disease is not compromising experimental work. Here, ophthalmic conditions are reviewed in order to provide a survey of ocular disease in the rat both for veterinary ophthalmologists and for laboratory animal veterinarians and research workers.

Animals↗

PubMed2002

Altered adrenal gland cholesterol metabolism in the apoE-deficient mouse.

Previous studies suggest the hypothesis that apoE produced by adrenocortical cells modulates cellular cholesterol metabolism to enhance the storage of esterified cholesterol (EC) at the expense of cholesterol delivery to the steroidogenic pathway. In the present study, parameters of adrenal cholesterol metabolism and corticosteroid production were examined in wild type and apoE-deficient (apoe(-/-)) mice. Adrenal gland EC content and the EC/free cholesterol (FC) ratio in mice stressed by adrenocorticotropin (ACTH) treatment or saline injection were reduced in apoe(-/-) compared to apoe(+/+) mice. Relative to apoe(+/+) mice, apoE deficiency also resulted in increased levels of plasma corticosterone in the basal state, in response to acute or long-term ACTH treatment, and after a swim-induced neuroendocrine-directed stress test. Measurements of adrenal gland scavenger receptor class B, type I (SR-BI), LDL receptor, and LDL receptor related protein (LRP) levels and the activities of ACAT or HMG-CoA reductase showed no difference between genotypes. Apoe(-/-) and apoe(+/+) mice showed similar quantitative increases in LDL receptors, SR-BI, adrenal weight gain, and ACAT activities in response to ACTH, and both genotypes had similar basal plasma ACTH concentrations. These results suggest that the effects of apoE deficiency reflect events at the level of the adrenal gland and are specific to changes in cholesterol accumulation and corticosterone production. Further, these findings support the hypothesis that apoE acts to enhance adrenocortical EC accumulation and diminish corticosterone production.

Adrenal Glands↗

PubMed2002

SR-BI is required for microvillar channel formation and the localization of HDL particles to the surface of adrenocortical cells in vivo.

Scavenger receptor class B type I (SR-BI) mediates the selective uptake of HDL cholesteryl ester into liver and steroidogenic tissues. In steroidogenic cells, juxtaposed microvilli, or microvilli snuggled against the plasma membrane create microvillar channels that fill with HDL. Microvillar membranes contain SR-BI and are believed to be the site of HDL cholesteryl ester uptake. A recent study showed that SR-BI expression in insect cells elicits membrane structures that contain SR-BI, bind HDL, and closely resemble the ultrastructure of microvillar channels. In the present study we compared the ultrastructure of adrenal gland microvillar membranes in Srb1+/+ and Srb1-/- mice to test whether SR-BI is required for the formation of microvillar channels. The results show that SR-BI is absolutely required for microvillar channel formation and that the microvillar membranes of Srb1-/- mice are 17% thinner than in Srb1+/+ mice. We conclude that SR-BI has a major influence on plasma membrane ultrastructure and organization in vivo.

Adrenal Cortex↗

PubMed2002

Human vascular endothelial cells express pattern recognition receptors for fungal glucans which stimulates nuclear factor kappaB activation and interleukin 8 production. Winner of the Best Paper Award from the Gold Medal Forum.

Fungal cell wall glucans nonspecifically stimulate various aspects of innate immunity via interaction with membrane receptors on macrophages, neutrophils, and natural killer cells. We investigated the binding of water-soluble glucans in primary cultures of normal human coronary or dermal vascular endothelial cells (VECs). Membranes from VECs exhibited saturable binding. Competition studies demonstrated the presence of at least two glucan binding sites on VECs. Glucan phosphate competed for all binding sites with a KD of 3.7 microM for coronary VECs and 11 microM for dermal VECs, respectively. Laminarin, a low molecular weight glucan, competed for 47 to 51 per cent of binding (KD = 2.8-2.9 microM), indicating the presence of at least two binding sites. Glucan (1 microg/mL) stimulated VEC nuclear factor kappaB nuclear binding activity and Interleukin 8 expression--but not that of vascular endothelial growth factor--in a time-dependent manner. This is the first report of pattern recognition receptors for glucan on human VECs. It also provides the first evidence that glucans can directly modulate the functional activity of VECs by stimulating cytokine gene. These results provide new insights into the mechanisms by which the host recognizes and responds to fungal cell wall products and suggests that the response to glucans may not be confined to leukocytes.

Antigens, Fungal↗

PubMed2002

Human monocyte scavenger receptors are pattern recognition receptors for (1-->3)-beta-D-glucans.

Glucans are cell wall constituents of fungi and bacteria that bind to pattern recognition receptors and modulate innate immunity, in part, by macrophage activation. We used surface plasmon resonance to examine the binding of glucans, differing in fine structure and charge density, to scavenger receptors on membranes isolated from human monocyte U937 cells. Experiments were performed at 25 degrees C using a biosensor surface with immobilized acetylated low density lipoprotein (AcLDL). Inhibition of the binding by polyinosinic acid, but not polycytidylic acid, confirmed the interaction of scavenger receptors. Competition studies showed that there are at least two AcLDL binding sites on human U937 cells. Glucan phosphate interacts with all sites, and the CM-glucans and laminarin interact with a subset of sites. Polymer charge has a dramatic effect on the affinity of glucans with macrophage scavenger receptors. However, it is also clear that human monocyte scavenger receptors recognize the basic glucan structure independent of charge.

Binding Sites↗

PubMedDate not supplied

Glucan stimulates human dermal fibroblast collagen biosynthesis through a nuclear factor-1 dependent mechanism.

Glucan, an immunomodulator, has been reported to increase collagen deposition and tensile strength in experimental models of wound repair. Previous data suggest that glucan modulates wound healing via an indirect mechanism in which macrophages are stimulated to release growth factors and cytokines. However, recent data have shown the presence of glucan receptors on normal human dermal fibroblasts, suggesting that glucans may be able to directly stimulate fibroblast collagen biosynthesis. To test this hypothesis, we examined the effect of glucan on collagen biosynthesis in normal human dermal fibroblasts. We assessed nuclear factor-1 (NF-1) activation, procollagen mRNA expression, collagen biosynthesis, and whether there was a causal link between glucan treatment, NF-1 activation, and collagen expression. Glucan (1 microg/ml) increased NF-1 binding activity by 46% (8 hours), 64% (24 hours), 215% (36 hours), and 119% (48 hours) in cultured normal human dermal fibroblasts. Alpha 1(I) and alpha1 (III) procollagen mRNA were increased in glucan-treated normal human dermal fibroblasts when compared with the untreated fibroblasts. Collagen synthesis was increased at 24 hours and 48 hours following glucan treatment of normal human dermal fibroblasts. Down-regulation of NF-1 by pentifylline inhibited glucan-induced procollagen mRNA expression. These data indicate that glucan can directly stimulate human fibroblast collagen biosynthesis through an NF-1-dependent mechanism.

Adjuvants, Immunologic↗

PubMedDate not supplied

Lens morphometry determined by B-mode ultrasonography of the normal and cataractous canine lens.

PURPOSE: To determine axial lens thickness, anterior chamber depth and axial globe length in canine eyes with normal lenses and in eyes with immature, mature, congenital, posterior polar and diabetic cataract. METHODS: B-mode ultrasonography was performed in 50 normal dogs and, as a prephacoemulsification screening procedure, in 100 dogs with cataract. Axial B-mode ultrasonograms were used to determine lens thickness, anterior chamber depth and globe diameter. Statistical comparisons between groups were made by analysis of variance and multivariate analysis, with a significance level of P < 0.05. RESULTS: Axial globe lengths were not statistically significantly different between groups apart from the smaller globes in younger dogs with congenital cataract. Axial lens thickness in diabetics (8.4 +/- 0.9 mm) was statistically significantly different from the lens thickness in normal eyes (6.7 +/- 1.0 mm), eyes with immature cataract (6.4 +/- 0.8 mm) and eyes with mature cataract (7.4 +/- 0.9 mm) although these groups, while varying in thickness, were not statistically significantly different from each other. Anterior chamber depth was statistically significantly reduced in eyes with diabetic cataract (2.9 +/- 0.1 mm) from that in normal eyes (3.8 +/- 0.1 mm), eyes with immature cataract (3.5 +/- 0.1 mm) and eyes with mature cataract (3.2 +/- 0.6 mm) although these groups, while varying in chamber depth, were not statistically significantly different from each other. CONCLUSIONS: Lenses with diabetic cataracts were significantly increased in axial thickness compared to lenses in other eyes, although lenses with mature cataracts showed a trend towards increased axial thickness and immature cataracts demonstrated a trend towards reduced thickness. While previous studies on cataract pathobiology have suggested a reduction in lens thickness in immature cataract through lens protein loss and an increase in thickness in mature cataracts through intumescence, this study is the first to document these changes in the canine lens.

Animals↗

PubMedDate not supplied

Entropion correction by fornix-based suture placement: use of the Quickert-Rathbun technique in ten dogs.

The objective of this study was to evaluate fornix-based suture placement as a method for entropion correction in the dog. Lower eyelid entropion with resultant trichiasis was corrected in 10 dogs using fornix-based suture placement similar to that employed in the Quickert-Rathbun technique used in man. A double-ended suture was placed originating at the deepest extent of the fornix and exiting the lid 1-2 mm from the eyelid margin. Degree of correction was assessed visually immediately after surgery and at re-examination with a follow-up period of up to 6 months. Fornix-based suture placement led to immediate eversion of the eyelid in each case and thus amelioration of the trichiasis in all dogs. In two cases eyelid eversion initially appeared over-corrected and in two cases exposure of conjunctival tissue was evident initially at the palpebral margin. In all cases, however, such complications were transient with long-term results giving an acceptable apposition between ocular surface and eyelid margin in all adult dogs. In three juvenile dogs on which the technique was used, further surgical treatment was required as the puppies grew. Fornix-based suture placement is a novel approach to entropion correction in the dog which yields acceptable results in the majority of suitable cases without recourse to incisional surgery.

Animals↗

PubMedDate not supplied

Analysis of tear uptake by the Schirmer tear test strip in the canine eye.

OBJECTIVE: To analyze the uptake of tears in a Schirmer tear test (STT) in vitro and in vitro. MATERIALS AND METHODS: Uptake of fluid by Schirmer tear test strips was studied in vitro by examining fluid uptake over time from an unlimited fluid supply as well as with specific fluid volumes applied to the test strip. Uptake of fluid by Schirmer tear test strips was evaluated in a population of 100 ophthalmologically normal dogs together with a group of 40 dogs with tear film abnormalities such as keratoconjunctivitis sicca (KCS) or epiphora. Each animal was given a full ophthalmic examination followed by a standard Schirmer tear test extended over between 3 and 5 min with the STT reading recorded every 5 s and plotted over time. To determine the effect of ocular irritation by the test strip, uptake of tears by test strips was determined before and after topical anesthesia in 20 dogs. RESULTS: In vitro examination of fluid uptake by the STT strips showed an initial rapid uptake followed by a gradual reduction in rate of uptake. Temporal evaluation of STT in vivo showed a similar rapid initial uptake of tear fluid, followed in the majority of cases by a sudden change to a steady state uptake of fluid. The initial gradient was 29.3 +/- 16.9 mm/min followed by a steady state uptake of 5.2 +/- 2.3 mm/min in normal dogs and 1.9 +/- 1.3 mm/min in dogs with KCS. This corresponds to a steady state tear turnover of 7.8 +/- 3.4 microL/min in normal dogs and 2.8 +/- 1.9 microL/min in animals with KCS. Dogs with nasolacrimal blockage and resultant epiphora showed a high initial gradient but final gradients were not statistically different from those of normal dogs. Discussion and conclusions Temporal evaluation of tear uptake by the STT shows substantial differences in rate of tear uptake at different time-points during the period of the test. RESULTS: of this study suggest that the initial rapid rise in STT value represents uptake from the tear lake followed by a slower tear uptake of tears from steady state tear production. Temporal examination of the Schirmer tear test allows a more precise evaluation of tear production than the standard STT measuring tear uptake in 1 min, together with estimation of the contribution to the test strip tear uptake of tears from the residual tear lake volume and those from continual tear production.

Absorption↗

PubMedDate not supplied

Effect of age, gender, weight, and time of day on tear production in normal dogs.

OBJECTIVE: To investigate the effects of age, weight, gender, and of time of day on tear production in normal dogs. ANIMALS: studied One hundred ophthalmoscopically and systemically unremarkable dogs. PROCEDURE: Schirmer tear tests (STT) were performed every 2 h during the day on one randomly chosen eye of each of 100 dogs. RESULTS: There was a statistically significant effect of time of day and age on the STT measurement. The mean STT decreased by 0.4 mm for every 1 year that age increased (P=0.007). Mean STT values taken at 10:00 am were 0.7 mm lower than values taken at 4:00 pm (P=0.04). CONCLUSIONS: Tear production decreases with age in the normal dog. In this population of dogs the largest difference was between the 10:00 am and the 4:00 pm STT measurements, but this still only amounted to 0.7 mm. This value is unlikely to be of clinical significance in the diagnosis of keratoconjunctivitis sicca (KCS).

Age Factors↗

PubMedDate not supplied

The effect of a topical antioxidant formulation including N-acetyl carnosine on canine cataract: a preliminary study.

OBJECTIVE: To determine the efficacy of a topical antioxidant formulation including N-acetyl carnosine in the treatment of canine cataract in a preliminary nonplacebo, controlled, unmasked study. ANIMALS STUDIED: Thirty dogs of varying breeds and ages with a spectrum of lens opacities ranging from nuclear sclerosis to total mature cataract. METHODS: Dogs were treated three times daily with topical 2% N-acetyl carnosine in a buffered vehicle containing the antioxidants glutathione, cysteine ascorbate, L-taurine and riboflavin (Ocluvet, Practivet, Phoenix, AZ, USA). Dogs were examined prior to treatment and at 2, 4 and 8 weeks during treatment, by direct and indirect ophthalmoscopy and slit-lamp biomicroscopy after pharmacologic pupil dilation. Photographic documentation of lens opacity was achieved by retroillumination photography, with three photographs taken at each examination time-point. A lens opacification index (LOI), determined by integration of the grayscale level of each pixel across the image, was evaluated by computerized image analysis of digitized images. Alteration in mean LOI was determined for each animal, having normalized the initial LOI. RESULTS: Fifty-eight eyes of 30 dogs were evaluated, 22 with mature cataract, 13 with immature cataract, 9 with cataract associated with other intraocular disease such as uveitis and 14 with nuclear sclerosis alone. One dog was unilaterally anophthalmic after previous enucleation and one had a phthytic eye after previous uveitis-induced glaucoma. Image analysis showed a reduction in mean LOI in all cataract groups (mean resolution in opacity of 2.3 +/- 0.33% for all cataracts), although this was only statistically significant in those eyes with immature cataract (mean resolution of opacity 4.5 +/- 0.33%) or nuclear sclerosis (mean decrease in opacity 5 +/- 0.37%). Reduction in lens opacity was seen in eyes with mature cataract (0.5 +/- 0.4%) and in miscellaneous cataract associated with intraocular inflammation (1.3 +/- 0.4%), but these changes were not statistically significant. Owner evaluation of visual capability, however, suggested improvement in vision in 80% of cases by the end of the study. CONCLUSIONS: This study demonstrates some marginal reduction in lens opacification in a substantial number of cases of canine cataract with the use of a topical nutritional antioxidant formulation including N-acetyl carnosine. Lens opacification was improved with treatment in eyes with immature cataract or nuclear sclerosis while in eyes with mature cataract or cataract with associated intraocular inflammatory pathology less reduction was seen.

Administration, Topical↗