Lens and eye toxicity research最新文献

To characterize aging as a factor responsible for structural changes the retinae of 47 Wistar-derived albino rats and 50 pigmented rats of the Norway and BDE (Han) strains between the ages of 1 and maximal 36 month were examined by light and electronmicroscopy and analysed for changes in cell densities. In all 3 rat strains there was an overall decline in nuclear densities of outer layer nuclei by 38 - 50% and inner layer nuclei by 27 - 33% between the ages of 1 and 27 months. Over the same age-range the ganglion cell loss was comparable to the decline in the inner nuclear layer. Neuronal cell death occurred at all ages and was more pronounced in albino rats. Moreover, in albino rats, cones were more resistant than rods to destruction by age and ambient light. Age-related ultrastructural changes in the retinal pigment epithelial cells (RPE) were in both pigmented strains: (1) a substantial accumulation of lipofuscin, (2) an apparent thickening of the basement membrane and (3) absent or greatly enlarged pleomorphic basal infoldings. In up to 27-month old BDE (Han) and 36-month old Norway rats besides mature stage IV-melanosomes also stage III-melanosomes can be observed. Characteristic of RPE-cells in old rats of these two strains were also compound granules and compound melanosomes. In peripheral RPE-cells of albino rats premelanosomes can be sporadically detected up to 31 months of age. Age-related changes in retinal vessels were found in the superficial and deep capillary network. The only finding was a 2-3 fold increase in thickness of the capillary basement membrane.

Lomefloxacin (NY-198) is a chemotherapic agent from the new 4-quinolone group, acting on DNA gyrase system. Lomefloxacin (LFLX), as some other new 4-quinolone compounds are antimicrobials of potential use for ophthalmic application. A first approach on the oculotoxicity of LFLX is the main purpose of this study. Four concentrations of LFLX (10, 30, 100 and 300 micrograms/ml) were tested on the first subculture of pigmented rabbit corneal epithelial cells. Cell number, protein contents, neutral red stain and wound healing were evaluated. The results showed that the lower concentrations (10 & 30 micrograms/ml) had no effect while the highest one had a remarkable cytotoxic effect. Pharmacokinetic data show that peak values achieved in the cornea and other ocular structures are lower than 40 micrograms/g (0.3% topical application) and, on another hand, MIC values range from less than or equal to 0.05 to 16 micrograms/ml. So, these "critical" concentrations have no cytotoxic effects according to our results. Then, it is concluded that Lomefloxacin could be a useful drug for topical ophthalmic development.

Clinical application of a newly developed ANTERIOR EYE SEGMENT ANALYSIS SYSTEM was introduced. By this system, a Scheimpflug and a retroillumination image of the anterior eye segment are obtained through a CCD camera, separately. To overcome difficult problems experienced with previous types of lens documentation systems, several kinds of new mechanisms were built into this system. Slit and retroillumination images of some cases with cataracts and some examples of anterior eye segment analysis were described.

The cholesterol requirements of the lens for the formation of plasma membranes are met by self-synthesis immediately after birth, this capacity, however, decreases considerably with increasing age, so that the deficit can only be met by exogenous supply. These findings are of great importance with respect to the qualitative assessment of extra-hepatical side effects of the substance class of HMG-CoA-reductase inhibitors on possible disturbances of lens transparency. In contrast to investigations of Mosley et al. (23) with rat and rabbit lenses, we did not find any activity of the HMG-CoA-reductase in our experiments with the lens cortex of calf, bovine, Beagle dog. The disturbances in lens transparency observed in chronical toxicity tests with high doses of HMG-CoA- reductase inhibitors might rather be due to the impairment of the exogenous cholesterol supply by a considerable decrease of the normal cholesterol level in the blood. The therapeutical treatment of pathologically increased blood cholesterol levels of patients should therefore not affect the transparency of human lenses. Relevant drug-safety-clinical studies confirm this experimentally substantiated supposition.

Corneal buttons obtained from keratoplasty were examined by energy dispersive x-ray analysis (EDXA) combined with scanning electron microscopy (SEM). This method enables to assay the mineral composition of minute parts of tissue samples identified in SEM images. Samples were cut from paraffin embedded corneae, deparaffinized in xylol, dried in aceton, critical-point desiccated, covered by evaporating with a thin layer of carbon and examined by SEM. In healthy human donor eyes, only some iron particles had been found. In the 22 patients samples high amounts of different particles were identified, materials from rubber stoppers, chromesteel, titanium pigments, talcum, barium and glass. Furthermore a lot of different metal particles containing varying amounts of Na, Mg, Al, Si, P, S, Cl, K, Ca, Fe, Cu, Cr, Zn, La and Ce were detected. Some particles may be caused by the initial trauma, others by therapy. Such contaminations might have supported leucocyte and fibrocyte invasion increasing the inflammatory reaction in the burnt cornea.

The protein distribution of bovine, monkey, dog, human and rabbit aqueous humour (AH) was determined by capillary isotachophoresis (ITF). The main component was albumin, and components of lower concentrations were transferrin, IgA and IgG. The results of the analysis by ITP were confirmed by immunoelectrophoresis. The appearance of the ITP patterns of normal AH's from 5 species was almost identical, the same main components were present in the AH of each species. When the blood/AH barrier was disrupted, the protein composition of the AH was changed abruptly. ITP was the technique of choice to determine quantitative changes in protein composition of the AH's. In rabbit secondary AH, ITP showed high proportions of albumin and enhanced concentrations of transferrin. Examples were given of the difference between early and late aspiration in bovine and rabbit. The ITP was thus the method of choice to confirm whether the blood/aqueous humour barrier was intact or damaged by the influence of a drug, given to experimental animals.

As the UV-B cataract and early stages of diabetic cataract in rats only touches the epithelium and anterior superficial cortex, a whole lens analysis is not meaningful, but a regional analysis with the freeze-sectioning device has to be performed. Scheimpflug photography with microdensitometric image analysis enables the scientist to discern in vivo single layers along the optical axis of the lens. UV-B cataracts (0.2 J/cm2, every 2nd day) and diabetic cataracts (Streptozotocin (STZ), 70 mg/kg BW) were induced in Brown-Norway rats. The stages of lens opacification were documented by Scheimpflug photography. 8 weeks after start of UV-B treatment and at several dates before onset of visible diabetic cataractous changes, the animals were sacrificed. The lenses were divided reproducibly into 4 or 7 parts such as an equatorial ring and several layers of the central cylinder from anterior to posterior part. The enzyme activity spectrum shows highly region related pattern that would not have been found in a whole lens analysis. Aldose reductase was activated before appearance of visible cataractous changes due to diabetes compared to normal lenses. In contrast Fructose-1,6-biphosphate-aldolase activity was lower before onset of visible changes than in normal lenses, but only within the 1st section where later visible cataractous changes of UV-B cataract could be detected.

The ophthalmoscopic examination of rats receiving drug administered by daily intravenous bolus injection for 6 months revealed an increase in the incidence and amplitude of linear irregularities in retinal blood vessels with a tendancy towards tortuosity which appeared to be related to treatment. Subsequent critical observation of groups of untreated rats, and rats dosed orally with a vasodilator suggest this phenomenum may be related to haemodynamic mechanisms; and that more attention should be given to the dose volume administered intravenously in this species to avoid the detection of such ocular artefacts.

Borna disease virus (BDV) infection, naturally occurring in horses and sheep induces a mononuclear retinitis and meningoencephalitis in adult Lewis rats. In the pathogenesis a virus-specific cell mediated immune reaction presumably of delayed hypersensitivity type is operative. Corresponding to the encephalitic lesions a progressive retinitis with loss of the first and second retinal neuron develops. The inflammatory response is characterized by predominance of macrophages in the early phase of infection followed by distinct plasmacellular infiltration. Immunosuppressed and immuno-incompetent rats do not develop retinal lesions after intracerebral inoculation. Thus similar as in the brain probably virus specific immunopathological reactions play a crucial role in the pathogenesis of BDV-induced retinitis in Lewis rats.

In a case of silver nitrate injury after Credé's prophylaxis, the cornea of a newborn presented yellow-brown, lime-like plaques on the nasal part of the right eye. A paracentral ulcerating stromal opacification undermined these appositions, when the patient was admitted to the eye-clinic at Aachen. In the material obtained by a lamellar keratectomy scanning electron microscopical examination was able to prove the existence of granules, previously described in light-microscopy. These granules measured 100 to 300 nm in diameter. An earlier chemical analysis of necrotic material showed no silver specific reaction. By means of EDX-analysis these granules could be identified as silver-containing. Injuries by silver nitrate solutions used for Credé's prophylaxis are seldom but still reported. The mechanism of injury in this case of a child, born by sectio remains unknown. Neither the use of an unusual silver nitrate solution, that was taken from a disposable ampoule (Mova-Nitrat R) was reported, nor any corneal injury during sectio mentioned. Nevertheless the method of EDX-analysis and SEM proved the diagnosis of corneal silver deposits, so that the origin of the granullar opacification of the cornea could be determined.