Lens and eye toxicity research最新文献

Beta-cyclodextrins are cyclic molecules with a hydrophilic outer side and a central hydrophobic cavity. Through the inclusion of drug molecules into their cavities, i.e. the formation of inclusion complexes, cyclodextrins are able to modify the physical and chemical properties of these molecules. When used in pharmaceutical formulations, they can improve the aqueous solubility, stability, dissolution rate, bioavailability and/or local tolerance of certain drugs. To make an initial evaluation of the potential use of beta-cyclodextrins as vehicles in ophthalmic eye-drop formulations, we studied the effect of a single and of multiple applications of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) 12.5% and of dimethyl-beta-cyclodextrin (DM-beta-CD) 5 and 12.5% solutions on the corneal epithelium of albino and pigmented rabbits with slit lamp biomicroscopy (SLB) and scanning electron microscopy (SEM). We can conclude from this study that DM-beta-CD at concentrations of 5 and 12.5% is not a suitable vehicle for ophthalmic formulations since it is toxic to the corneal epithelium and that HP-beta-CD at a concentration of 12.5% is well tolerated by the rabbit eye and is not toxic to the corneal epithelium when evaluated by SLB and SEM.

The elemental distributions in frozen-hydrated rat lenses with galactose cataract were compared before and after the onset of the nuclear cataract to investigate the possible role of ion levels in the lens opacification due to the phase separation of the lens cytoplasm. The maps of the weight concentrations of the minor elements, S, Cl, K and Ca, on the basis of wet weight in the central plane of lens were obtained by X-ray analysis with the high energy ion microprobe at a resolution of 50 microns. Before the onset of the nuclear cataract, the distributions of Cl and K, were almost normal, except in the lens posterior periphery with high Cl and low K. In the lens with the nuclear opacity, sudden changes were observed. The Cl increased throughout the lens, and K decreased throughout the lens except at lens anterior thin layer. However, the totalized monovalent ion level changed only slightly. The Ca level increased throughout the lens after the onset of the nuclear cataract, suggesting a possible role of Ca in the nuclear opacification of galactose cataract of rats. The distributions of S were similar to the protein density distributions previously known both in the normal and in the cataractous lenses.

When monitoring for drug induced lenticular side effects and/or anti-cataract drug efficacy, it would be advantageous to detect such effects prior to the onset of a cataract. Our MRI technique can detect precataractous changes in the lens water compartments (T2 values) months to years before opacities become manifest. The in vivo human and animal studies correlate well with in vitro NMR pulse relaxation data on such lenses. The MRI technique requires 2-4 minutes per eye and provides excellent pictures of the globe as well as T2 values. These data correlate well with our in vivo lens fluorescence technique thereby providing two parameters capable of evaluating potential drug induced changes in the lens well before the cataract becomes manifest.

In a randomised, prospective, parallel, double-masked study we examine the surface anesthetic effect of Bupranolol 0.25% in an oily solution. Bupranolol 0.25% decreases the corneal sensitivity to 23 mg/S, with the maximum between the 6th and 15th minute after application.

Cu-catalyzed oxidation of ascorbate has been studied in the absence and the presence of superoxide dismutase, catalase, mannitol, glycerol, ethanol, formate, and thiourea. None of these agents except thiourea inhibited the reaction. Therefore, the role of the Haber-Weiss reaction in the ascorbate oxidation could not be demonstrated. Electron spin resonance studies demonstrated that the preventive effect of the thiol is primarily due to the chelation of the reduced copper ions with the sulphur atom. The oxidation was also prevented by the chelation of copper with physiological levels of bovine serum albumin. These observations are consistent with the concept that a metal-oxygen complex is perhaps directly involved in the oxidative process. Measurements of the peroxide produced during oxidation indicated that significant amounts of this compound accumulates only at lower levels of ascorbate and in the absence of a protein or other chelating agents. At higher ascorbate levels no peroxide accumulation takes place. These results are, thus, useful in predicting the conditions under which the nutrient may act as a pro-oxidant or as an anti-oxidant. The observations suggest that under normal conditions low levels of ascorbate may act as a pro-oxidant through H2O2 production if the system has transition metal ions devoid of chelating agents. At higher concentrations ascorbate acts predominantly as an antioxidant.

Silicone oils, varying by viscosity and manufacturer, were infused into rabbit anterior chambers. Polydimethyl-siloxane oil, 5000 cps, increased corneal endothelial permeability to inulin (mw 5000) and dextran (mw 60000) when measured in vitro at 1, 4 and 7 days after ocular infusion. The effects of five other oils were measured at 7 days after infusion. Four of the oils increased endothelial permeability and induced similar morphological changes. Dow Corning Medical Fluid 360 had no effect on either permeability or morphology of the endothelium. These results show that contact of most silicone oils with corneal endothelium rapidly induces physiological and morphological changes. If these oils, when used as a retinal tamponade, gain access to the cornea they should be removed quickly to avoid the rapid initiation of physiologic changes.

In the years 1988 and 1989, routine ophthalmological examinations of dogs from the company-owned beagle colony revealed a clinically inapparent chorioretinitis in 7.4 and 10% of the animals, respectively, as it has previously been described by Weisse et al. (1981). The alterations were seen mainly in the non-tapetal fundus, and they appeared more frequently in both eyes than in just one eye. Infection tests as well as virologic, bacteriologic and histopathologic investigations were performed in order to clarify the origin. A direct evidence of virus particles from processed ocular material by electron microscopy was not possible. Tests for growth on MDCK cells were negative. In bacteriologic tests, a gram positive, filiform, branched microorganism was isolated. The histopathologic findings in the subacute stage were a focal atrophy of the first retinal neuron and a focal proliferation of glia cells.

With an increasing number of in-vivo methods to examine the eyes of laboratory animals, the rat has become an important animal model in experimental eye research. Specular microscopy is a clinical tool to examine the corneal endothelium in-vivo. To evaluate the versatility of this method for small animal eyes, we studied both corneal endothelial cell-count and corneal thickness in normal rats as well as those with diabetic, naphthalene and UV-B cataract. As a reference scanning electron microscopy (SEM) of the corneal endothelium was performed. For cell-counts the correlation coefficient between both methods was found to be sufficient. The comparison of corneal thickness measurement (SEM-values) with specular microscopy and with Scheimpflugbiometry failed to show a satisfactory correlation. The study proves that specular microscopy is a useful tool to document changes also in the endothelium of the rat-cornea.

Normal bovine lenses and bovine lenses after incubation in TC 199 in the presence of a lipid lowering drug were divided into four parts: the equatorial ring, the nucleus, the anterior cortex and posterior cortex. The lipids were extracted according to Egge et al. (1). Total lipids were determined gravimetrically, the lipid fractions phospholipids (PL), cardiolipin (CL), free fatty acids (FFA) and cholesterol (CH) were separated by thin layer chromatography and determined quantitative by densitometry after charring with 10% sulfuric acid. There are differences in lipid distribution between the four lens compartments, but there are no differences between normal and drug treated lenses in total lipids and lipid fractions. This result could be explained in different ways: either during this incubation time of 24 hours at 37 degrees C there will be no effect on the lens epithelial cells or there is no de-novo synthesis of lipids, especially of cholesterol in the bovine lens epithelium which could be influenced by lipid lowering drugs like HMG-CoA reductase inhibitors.