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Biomedical subjects

U Pleyer

Publications and source records attributed to U Pleyer.

At least 73 records · Page 4Linked to original sources
PubMed2000

Mediation of calcium-independent contraction in trabecular meshwork through protein kinase C and rho-A.

PURPOSE: Inhibition of protein kinase C (PKC) and rho-kinase (ROCK) may represent a new way of influencing outflow facility through isolated relaxation of the trabecular meshwork (TM). This work was performed to investigate the existence of calcium-independent contraction in this smooth-muscle-like tissue and its modulation by targeting the rho-guanosine triphosphatase (GTPase)-mediated pathway. METHODS: Isometric tension measurements of bovine TM and ciliary muscle (CM) were performed. Intra- and extracellular calcium buffering was accomplished with EGTA and 1, 2-bis(2-aminophenoxy)-ethane-N,N:,N:,N:',N:'-tetra-acetic acid tetrakis/acetoxymethhyl ester (BAPTA-AM) followed by stimulation of PKC with phorbolester (PMA) or 4alpha-phorbol. Calcium-independent contraction was blocked using the highly specific ROCK inhibitor Y-27632. Western blot analysis and immunoprecipitation was performed using human TM cells. RESULTS: In TM, carbachol induced partial contraction under conditions of extracellular calcium depletion (22. 1% +/- 2.3% versus 100%, n = 9). The membrane-permeable calcium chelator BAPTA-AM completely blocked this response (1.1% +/- 1.4% versus 100%, n = 9). When calcium was completely blocked, PMA induced contraction in TM (16.7% +/- 5.9% versus 100%, n = 9) but not in CM (1.8% +/- 2.5% versus 100%, n = 6). The inactive PMA analogue 4alpha-phorbol did not induce contraction, indicating that activation of PKC is involved in this contractile response. The ROCK inhibitor Y-27632 completely blocked the calcium-independent PMA-induced contraction in TM. Western blot analysis and immunoprecipitation revealed the expression of the rho-A protein in human TM cells. CONCLUSIONS: The data indicate that contrary to CM, the TM features calcium-independent contractile mechanisms linked to rho-A and PKC isoforms that do not require calcium for activation. ROCK inhibitors may allow specific modulation of the TM to enhance outflow facility, thus lowering intraocular pressure.

Amides↗
PubMed1999

Compound-heterozygous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis.

Homozygous type I plasminogen deficiency has been identified as a cause of ligneous conjunctivitis. In this study, 5 additional patients with ligneous conjunctivitis are examined. Three unrelated patients (1 boy, 1 elderly woman, and 1 man) had plasminogen antigen levels of less than 0.4, less than 0.4, and 2.4 mg/dL, respectively, but had plasminogen functional residual activity of 17%, 18%, and 17%, respectively. These subjects were compound-heterozygotes for different missense mutations in the plasminogen gene: Lys19 --> Glu/Arg513 --> His, Lys19 --> Glu/Arg216 --> His, and Lys19 --> Glu/Leu128 --> Pro, respectively. The other 2 patients, a 14-year-old boy and his 19-year-old sister, who both presented with a severe course of the disease, exhibited plasminogen antigen and functional activity levels below the detection limit (<0.4 mg/dL and <5%, respectively). These subjects were compound-heterozygotes for a deletion mutation (del Lys212) and a splice site mutation in intron Q (Ex17 + 1del-g) in the plasminogen gene. These findings show that certain compound-heterozygous mutations in the plasminogen gene may be associated with ligneous conjunctivitis. Our findings also suggest that the severity of clinical symptoms of ligneous conjunctivitis and its associated complications may depend on the amount of plasminogen functional residual activity.

Adolescent↗
PubMed1999

Delayed mustard gas keratopathy: clinical findings and confocal microscopy.

PURPOSE: To describe the clinical manifestations and confocal microscopic findings in a patient with delayed mustard gas keratopathy. METHOD: Case report. A 32-year-old veteran who had participated in the Iran Iraq conflict was exposed to mustard gas in 1988. Ocular abnormalities in 1996 and 1998 and corneal confocal microscopic findings in 1998 are presented. RESULTS: In 1996, slit-lamp examination disclosed bilateral limbal changes with tortuous blood vessels and full-thickness corneal alterations. In 1998, the right eye had porcelain-white episcleral changes and adjacent peripheral ulcerative keratopathy. Confocal microscopy demonstrated irregular-appearing epithelial and basal epithelial cells. The anterior stroma was remarkable for spindle-like keratocytes, diffuse fibrillar inhomogeneities and the presence of highly reflective material. CONCLUSIONS: Mustard gas keratopathy is a uncommon cause of ocular damage, but it may lead to delayed ocular damage.

Adult↗
PubMed1999

[Confocal microscopy in corneal dystrophies].

BACKGROUND: Confocal microscopy represents a methodology that allows in vivo examination of corneal morphology, particularly of the epithelium and stroma. MATERIAL AND METHODS: Using the confocal microscope "ConfoScan Modell P2" epithelial, stromal and endothelial changes were evaluated in 11 patients with corneal dystrophies. All findings were compared with data from healthy individuals. RESULTS: Confocal images could be correlated to conventional (slitlamp) biomicroscopic findings in all patients with corneal dystrophies. In addition, confocal microscopy provided more detailed images particularly of epithelial and stromal changes. CONCLUSION: Our data indicate that confocal microscopy provides information on living tissue that correlates with that obtained with conventional techniques on fixed and sectioned tissue.

Corneal Dystrophies, Hereditary↗
PubMed1999

[Modulation of immune mediated diseases of the eye].

The eye is the target of a variety of immune mediated diseases. Advances in the field of immunology have permitted a better understanding of these challenges. This progress has been accompanied by the development of more specific immunomodulating agents. Corticosteroids are still a major agent in the management of ocular immunomediated diseases, but are now supplemented by other potent immunomodulating agents. The excitement in pharmacological research has in turn provided more insight in immune mechanisms and some of the newer agents have been used as "probes" for a better understanding of basic mechanisms. In order to better evaluate the indications of certain agents, the properties of established and forthcoming agents are presented. The field of immunopharmacology includes a multitude of preclinical areas related to the development of immunotherapy and immunotoxicology. This review attempts to address some topics of the current knowledge of the use of immunomodulating agents in ophthalmology.

Animals↗
PubMed1999

Influence of cyclodextrins on the in vitro corneal permeability and in vivo ocular distribution of thalidomide.

The aim of the present study has been to develop aqueous Thalidomide (THA) eye drops in order to minimize systemic side effects and to improve bioavailability following topical application. Cyclodextrins (CDs), suitable vehicles to improve aqueous solubility of THA, were evaluated with regard to their ability to influence in vitro corneal permeability of THA. Additionally, rabbit eyes received either THA-suspension (0.04%) (THA-SP) or THA (0.04%)/hydroxypropyl-beta-cyclodextrin (HP-beta-CD) (12.5%) solution (THA-CD). In vitro corneal permeation studies demonstrated that the absolute amount of THA permeated could not be increased by means of CDs. The percentile release of THA was extensively decreased using saturated THA/CD solutions. Following loading doses of either THA-CD or THA-SP onto the rabbit eye, significantly increased aqueous humor levels were obtained for THA-CD 30 min (THA-CD:THA-SP=4.6:1) and 60 min (THA-CD:THA-SP=3.1:1) post instillation (p<0.05). In the iris-ciliary body, significantly increased THA levels were obtained using THA suspension (THA-CD(60 min):THA-SP(60 min)=1:6.1) (p<0.05). In the cornea, conjunctiva, vitreous and sclera, differences between the THA tissue levels were not statistically significant. Cyclodextrins might be a useful tool to formulate aqueous THA eye drop solutions and modify intraocular drug bioavailability.

Angiogenesis Inhibitors↗
PubMed1999

Experimental intravitreal application of ciprofloxacin in rabbits.

BACKGROUND: Ciprofloxacin (CFLX) is a fluoroquinolone antibiotic with a broad antimicrobial spectrum. This study was performed to examine the retinal toxicity of free and liposome-incorporated CFLX in rabbit eyes after intravitreal injection. MATERIALS AND METHODS: Free CFLX in doses of 100, 250, 500, 1,000 and 2,000 microg was injected into the midvitreous of rabbit eyes (n = 28). To prolong the intravitreal antibacterial level, CFLX was incorporated into multilamellar liposomes: 0.1 ml of this suspension ( wedge 273.6 microg CFLX) was injected into the midvitreous of a second group of rabbit eyes (n = 6). The other eye served as a control and received normal saline solution or empty liposomes, respectively. Before injection and at the end of follow-up an electroretinogram (ERG) was obtained. After a follow-up of 1, 14 and 28 days the animals were perfused with glutaraldehyde and the eyes were examined by light and transmission electron microscopy. RESULTS: Significant reduction of the ERG was observed after 2,000 microg free CFLX in 4 out of 6 eyes after 14 days. Fourteen days after injection of 2,000 microg CFLX the central retina showed pigmentary changes in 4 out of 6 eyes. In the second group the ERG as well as the histologic studies did not reveal any pathologic changes after injection of liposome-incorporated CFLX compared to the control eyes. CONCLUSION: In therapeutic doses of 100-500 microg, free CFLX does not have retinal toxicity in rabbit eyes. No retinal toxicity was observed after intravitreal injection of liposome-incorporated CFLX.

Animals↗
PubMed1998

[Pseudophakia in children with juvenile arthritis].

BACKGROUND: Cataract secondary to juvenile rheumatoid arthritis is a severe, vision-threatening complication in early childhood. Intraocular lens implantation is controversial. The follow-up of four pseudophakic eyes of three patients and their perioperative therapeutic regimen were retrospectively analyzed. Early and late postoperative complications are reported. PATIENTS AND METHODS: Both girls had lens aspiration and posterior lens implantation at the ages of 6 and 12 years, the boy at the age of 10 and 14 years. All patients had relapsing anterior uveitis. The follow-up time was 3 years (1-6 years). One girl was diagnosed with sarcoidosis, causing juvenile arthritis. Both girls had perioperative methothrexate and prednisolone therapy. The boy had azathioprine therapy at the time of his first cataract surgery; later he had no systemic therapy. Both girls' intraocular lenses were implanted at different eye hospitals. RESULTS: Both girls had severe inflammatory reactions after surgery. At the hospitals both eyes had surgical revision for iris capture. In one case this was combined with exchanging the intraocular lens. Iris capture persisted for this eye and later vitrectomy with silicone oil filling was necessary to delay phthisis, resulting in amaurosis. For two pseudophakic eyes vitrectomy was necessary later because of severe vitreous opacities, but visual acuity was severely diminished by chronic cystoid macular edema and epiretinal membranes. The boy developed in his second eye intermittent iris bombata and persistent secondary glaucoma, visual acuity was stabilized at 0.5. CONCLUSIONS: Secondary cataract due to juvenile rheumatoid arthritis or sarcoidosis is a difficult situation for phacoemulsification with intraocular lens implantation in children. For severe inflammatory complications intense local and systemic anti-inflammatory therapy is mandatory. Visual prognosis is reduced for the uveitic posterior segment and glaucoma complications. IOL implantation can be recommended for only a very few patients.

Adolescent↗
PubMed1998

[Clearance of liposome-incorporated ciprofloxacin after intravitreal injection in rabbit eyes].

BACKGROUND: Ciprofloxacin (CIP) is a fluoroquinolone-antibiotic with a high antimicrobial activity against all pathogens causing bacterial endophthalmitis. After intravitreal injection, however, elimination half-life of this antibiotic is only 2.2 hours. To prolong intraocular bioavailability this study was performed to incorporate CIP into liposomes and to determine its clearance from the vitreous after intravitreal injection. MATERIALS AND METHODS: CIP was incorporated into multilamellar vesicles by mechanical dispersion. 0.1 ml of this suspension (equiv. 273.6 micrograms CIP) was injected into the midvitreous of pigmented rabbit eyes (Chinchilla-bastards). One day, 3 and 14 days after the injection intravitreal concentration of CIP was determined by means of high-pressure-liquid-chromatography after dissolution of the liposomes by ultrasound. At the same intervals serum concentration of the antibiotic was examined as well. RESULTS: Within 24 hours intravitreal concentration fell to 18.0 micrograms/ml. Three days after the injection the concentration of CIP was 6.9 micrograms/ml. This is still above the minimal inhibitory concentration (MIC90) of the most common ocular pathogens. At 14 days CIP was not detectable in the vitreous any more. The serum concentration was between 0.04 microgram/ml and 0.07 microgram/ml. 3 and 14 days after injection no CIP could be detected. CONCLUSIONS: This study shows that the incorporation of CIP into liposomes can be achieved in sufficient doses by mechanical dispersion method. After intravitreal application the bioavailability of the antibiotic can be markedly improved. Even after 3 days the intravitreal levels were above the MIC90 of the most common endophthalmitis pathogens.

Animals↗
PubMed1998

Topical liposome-encapsulated FK506 for the treatment of endotoxin-induced uveitis.

PURPOSE: Liposome preparations of FK506 improve the penetration of topically administered drug into the aqueous humor. The purpose of the experiment was to compare topically administered highdose oil-dissolved FK506 (OD-FK506) and low-dose liposome-bound FK506 (LB-506) for the treatment of endotoxin-induced uveitis (EIU). METHODS: Endotoxin-induced uveitis was produced in female Lewis rats with Salmonella typhimurium endotoxin. Four hours prior to endotoxin injection, one eye received 20 mul eyedrops every four hours containing either high-dose OD-FK506 at 3 mg/ml (N = 20), low-dose LB-FK506 at 0.16 mg/ml (N = 19), prednisolone acetate 1% (N = 20), or empty liposomes (N = 20). Eyes were enucleated 24 hours after endotoxin injection and inflammatory cells were counted on histologic sections by two masked observers. RESULTS: The mean number of infiltrating inflammatory cells per section +/- S.E.M. was 127.8 +/- 20.1, 76.8 +/- 16.7, 75.0 +/- 19.1, and 3.6 +/- 0.4 for animals treated with empty liposomes, LB-FK506, OD-FK506, and prednisolone acetate, respectively. The difference in inflammation between the empty liposome controls and the LB-FK506- and OD-FK506-treated animals was statistically significant (p = 0.03 and p = 0.02, respectively). The difference in inflammation between the high-dose OD-FK506- and low-dose LB-FK506-treated animals was not statistically significant (0 = 0.94). CONCLUSION: In this study, low-dose LB-FK506 and high-dose (OD-FK506) were both effective in inhibiting EIU. Higher concentrations of LB-FK506 are being developed and should augment the therapeutic effect of topical FK506.

Administration, Topical↗
PubMed1997

Antibacterial protection of the ocular surface.

The outer surface of the eye is constantly exposed to a wide array of microorganisms. To protect the integrity or the ocular surface and to retain corneal transparency, a number of defense mechanisms have evolved. This article discusses the host mechanisms of the eyelids-, tears, cornea and conjunctiva. These host defense mechanisms are identified as either a native, nonspecific defense or a specifically acquired immunological defense requiring previous exposure to an antigen and the development of specific immunity. Nonspecific components that protect the eye include the eyelids, ocular surface epithelium, normal flora and tear proteins. Specifically acquired immunity in tears, cornea and conjunctiva involves the interaction of antigen-presenting cells, lymphocytes and humoral components of the immune system.

Animals↗