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3.
Ophthalmologe ; 107(8): 715-9, 2010 Aug.
Article in German | MEDLINE | ID: mdl-20533042

ABSTRACT

The value of measuring the critical fusion frequency (CFF) as part of ophthalmological diagnostics is examined. The relevant literature on changes of the CFF concomitant with refraction errors, media opacity, age-related macular degeneration, glaucoma and various other opticopathies is discussed regarding the relevance of CFF for the differential diagnosis. Various methods and instruments for measuring the CFF are presented. The CFF is a complex function of the visual system and changes in CFF cannot be ascribed to a specific level of signal transduction. However, measurement of the CFF is a valuable test in the clinical routine to estimate potential visual acuity in the presence of media opacity and to screen for lesions of the optic nerve. Reduction of CFF in an eye that otherwise appears normal may prompt the ophthalmologist to initiate further examination facilitating diagnosis of specific conditions, such as optic neuritis, before visual acuity is reduced. Measuring the CFF is technically simple, inexpensive and fast and can be delegated to medical personnel. Measurement of the CFF should be an integral component of routine ophthalmological examinations.


Subject(s)
Eye Diseases/diagnosis , Flicker Fusion , Vision Disorders/diagnosis , Cataract/diagnosis , Diagnosis, Differential , Glaucoma/diagnosis , Humans , Macular Degeneration/diagnosis , Optic Neuritis/diagnosis , Refractive Errors/diagnosis , Vision Tests/instrumentation , Visual Acuity
4.
Klin Monbl Augenheilkd ; 226(8): 659-63, 2009 Aug.
Article in German | MEDLINE | ID: mdl-19468970

ABSTRACT

BACKGROUND: Peripheral exudative haemorrhagic chorioretinopathy (PEHCR) is a degenerative disease of the peripheral retina and choroid in the elderly. Although PEHCR is often seen by clinicians, this entity is underrepresented in the ophthalmological literature. This may be due to inconsistent naming. PATIENTS: We present the clinical, ultrasonographic and angiographic findings of 11 eyes of 8 patients who were diagnosed with PECHR in our department between January 2006 and June 2008. In addition, we report the intra- and postoperative course of three eyes that have been vitrectomised because of a vitreous haemorrhage associated with PEHCR. RESULTS: The mean age of the patients is 83.5 years (range: 75 - 95). The mean follow-up is 11 months (range: 0 to 20). The clinical and angiographic signs were dependent on the stage of the disease and may be seen as small asymptomatic peripheral subretinal bleeding and exudation. In advanced stages, vitreous haemorrhage and exudative retinal detachment may be observed. The temporal periphery of the fundus appears to be more often affected than other locations. Three patients were affected bilaterally. Vitreous haemorrhage was the reason for presentation in three eyes (27 %) that were treated successfully by vitrectomy. CONCLUSIONS: Peripheral exudative hemorrhagic chorioretinopathy should be considered in the differential diagnosis of vitreous haemorrhage and peripheral subretinal tumors in the elderly.


Subject(s)
Chorioretinitis/diagnosis , Choroid Hemorrhage/diagnosis , Exudates and Transudates/diagnostic imaging , Peripheral Vascular Diseases/diagnosis , Retinal Hemorrhage/diagnosis , Aged , Aged, 80 and over , Angiography , Female , Humans , Male , Syndrome , Ultrasonography
5.
Klin Monbl Augenheilkd ; 226(8): 654-8, 2009 Aug.
Article in German | MEDLINE | ID: mdl-19399715

ABSTRACT

BACKGROUND: An association of the Tyr402His variant of the complement factor H (CFH) gene with age-related macular degeneration (AMD) has been shown in several Caucasian populations, while studies for an association with other single nucleotide polymorphisms (SNP) of complement system genes have produced inconsistent results. We examined the distribution of several SNPs of complement system genes (CFH, C 2, C 3, factor B) in patients with exsudative AMD and healthy controls. PATIENTS/MATERIALS AND METHODS: 226 patients with exsudative AMD and 179 controls without AMD were included. Genomic DNA was extracted from saliva samples. RESULTS: A significant association with exsudative AMD was found only for SNP rs1061170 (Y402 H) in the CFH gene. For rs1047286 (P292L) and rs2230199 (R102G) in the C 3 gene, rs547154 (IVS10) and rs9332739 (E318D) in the C 2 gene and rs4151667 (L9 H) in CFB gene, no associations with exsudative AMD were found. CONCLUSIONS: We have replicated an association of the Y 402 H variant with exsudative AMD in our population. Although variants R 102G, IVS10, E 318D and L 9 H have been shown to be associated with AMD in earlier studies, we could not confirm these findings. The results show that AMD has variable association patterns with rare variants in different populations.


Subject(s)
Complement System Proteins/genetics , Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/genetics , Macular Degeneration/epidemiology , Macular Degeneration/genetics , Polymorphism, Single Nucleotide/genetics , Aged , Aged, 80 and over , Female , Genetic Markers/genetics , Germany/epidemiology , Humans , Male , Prevalence , Risk Assessment/methods , Risk Factors
6.
Klin Padiatr ; 220(5): 316-7, 2008.
Article in German | MEDLINE | ID: mdl-18651375

ABSTRACT

BACKGROUND: The prevalence of idiopathic intracranial hypertension is increased in overweight children and adolescents. CASE REPORT: In a fifteen-year old, extremely obese adolescent with a history of headache and diplopia treatment with acetazolamide resulted in relief of the neurological symptoms.


Subject(s)
Diplopia/etiology , Headache/etiology , Obesity, Morbid/complications , Papilledema/etiology , Pseudotumor Cerebri , Acetazolamide/administration & dosage , Acetazolamide/therapeutic use , Administration, Oral , Adolescent , Carbonic Anhydrase Inhibitors/administration & dosage , Carbonic Anhydrase Inhibitors/therapeutic use , Humans , Magnetic Resonance Imaging , Male , Pseudotumor Cerebri/complications , Pseudotumor Cerebri/diagnosis , Pseudotumor Cerebri/drug therapy
7.
Ophthalmologe ; 105(10): 927-30, 2008 Oct.
Article in German | MEDLINE | ID: mdl-18488231

ABSTRACT

BACKGROUND: To analyze changes in visual acuity after cataract surgery in patients suffering from age-related maculopathy. MATERIAL AND METHODS: This retrospective case-control study included all patients who had consecutively undergone phacoemulsification from January 2000 to February 2006, had a preexisting diagnosis of early age-related macular degeneration (AMD), and were followed up for at least 1 year postoperatively (n=1,152 eyes of 696 patients). The control group comprised phakic patients diagnosed with early AMD from January 2000 to February 2006 who did not undergo eye surgery and were followed up for at least 1 year (n=334 eyes of 202 patients). RESULTS: In 62.1% of operated eyes, the best-corrected visual acuity was at least two logMAR units better than before surgery, and in 26.7% it was at least four logMAR units better. Deterioration of visual acuity of more than four logMAR units occurred in 1.3% of operated eyes and 1.5% of control eyes. CONCLUSION: Cataract surgery can markedly improve visual acuity in patients with age-related maculopathy.


Subject(s)
Lenses, Intraocular , Macular Degeneration/surgery , Postoperative Complications/etiology , Visual Acuity , Cohort Studies , Comorbidity , Humans , Retrospective Studies
8.
Ophthalmologe ; 104(3): 243-5, 2007 Mar.
Article in German | MEDLINE | ID: mdl-17123051

ABSTRACT

BACKGROUND: The term 'frosted branch angiitis' was initially used to describe an idiopathic form of vasculitis in association with panuveitis. It has since also been used to describe the angiographic phenomenon of diffuse leakage along retinal vessels against the background of other ocular and systemic diseases. METHODS: We describe a 57-year-old male patient with acute bilateral reduction of visual acuity, headaches and absence of any pulse at the temporal arteries. Fluorescence angiography showed bilateral diffuse leakage along all the retinal vessels, which resembled frosted branches. Laboratory parameters and histology were not indicative of vasculitis. Imaging showed complete occlusion of both common carotid arteries and a hypoplastic vertebral artery on the left. CONCLUSIONS: Ocular ischemia may imitate primarily inflammatory conditions in its angiographic appearance.


Subject(s)
Eye/blood supply , Ischemia/complications , Ischemia/diagnostic imaging , Panuveitis/complications , Panuveitis/diagnostic imaging , Vasculitis/complications , Vasculitis/diagnostic imaging , Angiography , Eye/diagnostic imaging , Humans , Male , Middle Aged
9.
Klin Monbl Augenheilkd ; 223(9): 721-5, 2006 Sep.
Article in German | MEDLINE | ID: mdl-16986081

ABSTRACT

During the past years refractive surgical procedures and particularly laser IN SITU keratomileusis (LASIK) have become established by clinical and experimental studies and are performed worldwide in a high number. This paper provides a survey of the published posterior segment complications of LASIK that may occur albeit very rarely. Additionally, current clinical and experimental hypotheses regarding the pathogenesis of those complications are discussed. Currently a cause-effect relationship between LASIK and reported posterior segment complications has not been proven although a very high number of LASIK procedures have been performed worldwide.


Subject(s)
Choroid Diseases/etiology , Choroid/injuries , Eye Injuries/etiology , Keratomileusis, Laser In Situ/adverse effects , Retinal Detachment/etiology , Risk Assessment , Vitreous Detachment/etiology , Humans , Incidence , Risk Factors
10.
Eur J Ophthalmol ; 16(4): 618-20, 2006.
Article in English | MEDLINE | ID: mdl-16952105

ABSTRACT

PURPOSE: The surgical treatment of band keratopathy usually consists of abrasion of the corneal epithelium followed by removal of the subepithelial calcium deposits by means of an ethylenediamine-tetraacetic acid (EDTA) solution. In order to reduce the discomfort and pain that occur after corneal abrasion, the authors developed a modified technique that avoids the abrasion of the epithelium. METHODS: In three patients (four eyes) with long-standing band keratopathy, the epithelium was detached with a 19% ethanol solution and placed gently toward the limbus, a method also used in laser-assisted subepithelial keratectomy (LASEK). After clearing the anterior stroma with EDTA solution, the epithelial flap is unrolled and a bandage contact lens applied. RESULTS: Postoperative pain was greatly reduced and after removal of the contact lens no pain was reported. CONCLUSIONS: This modified epithelium-sparing treatment of band keratopathy shows good results while reducing postoperative pain.


Subject(s)
Calcinosis/therapy , Chelating Agents/therapeutic use , Corneal Diseases/therapy , Edetic Acid/therapeutic use , Ophthalmologic Surgical Procedures , Calcinosis/metabolism , Calcium/metabolism , Combined Modality Therapy , Corneal Diseases/metabolism , Humans
11.
Ophthalmologe ; 103(9): 765-72, 2006 Sep.
Article in German | MEDLINE | ID: mdl-16902806

ABSTRACT

Uveitis can be found in all age groups, but the age of disease onset may provide important information on the etiology of the disease. New data on the epidemiology of uveitis disclose a higher incidence and prevalence in older patients then has previously been found. Masquerade syndromes which mimic uveitis may be found especially in younger and older patients. These have to be excluded from regular intraocular inflammation. Here, intraocular lymphoma plays a major role which is most often associated with severe clinical, diagnostic and therapeutic challenges. One of the major complications of uveitis is cataract formation. Keeping in mind the importance of pre- and postoperative treatment, even implantation of an intraocular lens in older patients with uveitis is currently a safe procedure.


Subject(s)
Aging , Cataract/diagnosis , Cataract/therapy , Uveitis/diagnosis , Uveitis/therapy , Age Factors , Cataract/epidemiology , Comorbidity , Germany/epidemiology , Humans , Practice Patterns, Physicians'/trends , Uveitis/epidemiology
12.
Klin Monbl Augenheilkd ; 222(7): 586-9, 2005 Jul.
Article in German | MEDLINE | ID: mdl-16034727

ABSTRACT

BACKGROUND: Photodynamic therapy (PDT) and surgical macular translocation are concurrent treatment options for exudative age-related macular degeneration (ARMD). PDT is currently favoured because of positive study results and the non-invasive technique. We report a case of macular translocation with 360 degrees retinotomy after unsuccessful previous PDT for treatment of ARMD. CASE REPORT: PDT with verteporfin was performed in the left eye of a 79-year-old patient with exudative ARMD and predominantly classic juxtafoveal choroidal neovascularisation (CNV). Because of continuing visual loss and deteriorating angiographic signs three months after PDT, a surgical macular translocation with 360 degrees retinotomy was performed successfully. During the surgery increased adhesion between the CNV and the retina was observed in contrast to patients without previous PDT. In a second step three months later, counter-rotation of the ocular globe was achieved by muscle surgery and the silicone oil was removed in the same session. The best spectacle corrected visual acuity improved from 0.1 before the surgery to 0.4 nine months thereafter (six Snellen lines). No CNV recurrence was observed. Patient satisfaction with the surgery outcome is high. CONCLUSIONS: Macular translocation may be considered in cases of continuing deterioration after a previous PDT for treatment of exudative ARMD. Possible complications must be discussed with the patient. Intraoperatively, increased adhesion of CNV to the retina was observed, which might increase the risk of inadvertent damage to the retina during surgery.


Subject(s)
Hematoporphyrin Photoradiation , Macula Lutea/surgery , Macular Degeneration/drug therapy , Aged , Choroidal Neovascularization/diagnosis , Choroidal Neovascularization/surgery , Combined Modality Therapy , Fluorescein Angiography , Follow-Up Studies , Humans , Macular Degeneration/diagnosis , Male , Retina/surgery , Visual Acuity/physiology
14.
J Med Virol ; 73(2): 250-5, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15122800

ABSTRACT

A patient presented with acute retinal necrosis of the left eye. Demonstration of herpes simplex virus (HSV) DNA in the aqueous humour confirmed the diagnosis. Negative results of HSV type-specific antibody tests based on gG antigens suggested a primary HSV infection. However, the patient had a past history of laboratory-confirmed herpes simplex encephalitis 6 years ago. Using antibody tests based on whole viral lysate antigens, he was seropositive from the onset, and immunoblot testing confirmed a lack of anti-gG reactivity. To be able to assess whether this might be related to the apparent inability of his immune system to suppress clinically symptomatic HSV infection, serial samples were tested by an HSV neutralisation test and a whole-blood flow cytometric assay to determine the frequency of HSV-specific CD4 lymphocytes. However, this did not yield evidence of obvious immunodeficiency; the patient reacted similarly to known positive controls by both assays. Although type-specific HSV serological tests based on gG are generally more specific than those based on whole viral lysate antigens, they have a somewhat lower sensitivity, as a certain percentage of HSV-infected individuals do not develop antibodies against gG, and others may suffer a secondary loss of anti-gG reactivity. Thus there is a risk of missing individual infected patients. Unless this potential problem is recognised, serious consequences might possibly result. We therefore urge virologists and clinicians to exercise great care if highly specific antibody assays based on recombinant proteins are employed.


Subject(s)
Encephalitis, Herpes Simplex/complications , Encephalitis, Herpes Simplex/immunology , Retinal Necrosis Syndrome, Acute/pathology , Retinal Necrosis Syndrome, Acute/virology , Simplexvirus/isolation & purification , Antibodies, Viral/blood , Antigens, Viral/immunology , Aqueous Humor/virology , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , DNA, Viral/isolation & purification , Enzyme-Linked Immunosorbent Assay , Humans , Immunoblotting , Male , Middle Aged , Neutralization Tests , Viral Envelope Proteins/immunology
15.
Br J Ophthalmol ; 87(5): 548-50, 2003 May.
Article in English | MEDLINE | ID: mdl-12714388

ABSTRACT

BACKGROUND/AIMS: Ultrastructural alterations in the stroma adjacent to corneal perforations have previously been reported in patients with longstanding rheumatoid arthritis. Since patients with rheumatoid arthritis often present upregulation of proinflammatory cytokines in serum and in synovial fluid, it was of interest to analyse the gene expression of these cytokines-for example, tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), in corneal samples from patients with corneal ulcerations and/or perforations associated with rheumatoid arthritis. METHODS: Corneal samples from seven patients with corneal ulcerations and/or perforations associated with rheumatoid arthritis were collected in 4% paraformaldehyde in "RNAse-free" conditions. Paraffin sections were fixed on silan coated slides and further analysed by systematic non-radioactive in situ hybridisation, using specific gene probes for TNF-alpha and IL-6 labelled with digoxigenin (DIG). Detection of hybrids was carried out by using a commercially available DIG detection system. RESULTS: Whereas an extended TNF-alpha gene expression could be clearly observed in the keratocytes surrounding the corneal ulcerations and/or perforations from five of the seven analysed patients, all seven patients presented clearly positive results for an extended IL-6 gene expression in the analysed tissue samples. CONCLUSIONS: Alterations in corneal cells surrounding ulcerations and/or perforations in patients with rheumatoid arthritis may occur with implication for inflammatory processes. Upregulation of the proinflammatory cytokines TNF-alpha and IL-6 may modify the production of metalloproteinases in the corresponding cells resulting in collagenolytic corneal damage.


Subject(s)
Arthritis, Rheumatoid/genetics , Cornea/cytology , Corneal Ulcer/genetics , Tumor Necrosis Factor-alpha/analysis , Aged , Female , Gene Expression , Humans , In Situ Hybridization , Interleukin-6/analysis , Male , Middle Aged , RNA, Messenger/analysis
16.
Ophthalmic Res ; 35(3): 143-9, 2003.
Article in English | MEDLINE | ID: mdl-12711841

ABSTRACT

CG5601 is a novel immunomodulatory substance showing anti-inflammatory properties comparable to thalidomide. To investigate the anti-inflammatory effects of CG5601 in endotoxin-induced uveitis (EIU) and to evaluate its influence on leukocyte-endothelium interaction, the anterior chamber inflammatory reaction was assessed and intravital fluorescence microscopy was carried out at 2, 4, 8 and 24 h. Lewis rats received an intraperitoneal injection of CG5601 (200 mg/kg b.w.) at the time of lipopolysaccharide injection. At 8 and 24 h, CG5601 inhibited the cell migration and protein concentration in the aqueous humor compared to untreated EIU (p < 0.0001). There was no significant difference between nontreated animals and vehicle controls. The treatment of CG5601 reduced the number of rolling leukocytes. At early time points (2 and 4 h), inhibition of rolling leukocyte flux was significant (p < 0.005). The rise of serum TNF-alpha levels in EIU at 2 h was reduced. CG5601 exerts potent anti-inflammatory effects in EIU.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Uveitis/drug therapy , Animals , Aqueous Humor/metabolism , Disease Models, Animal , Drug Evaluation, Preclinical , Endotoxins , Female , Imidazoles/therapeutic use , Leukocyte Rolling/drug effects , Leukocytes/drug effects , Lipopolysaccharides/toxicity , Rats , Rats, Wistar , Spiro Compounds/therapeutic use , Thalidomide/analogs & derivatives , Thalidomide/therapeutic use , Thiazoles/therapeutic use , Time Factors , Tumor Necrosis Factor-alpha/metabolism , Uveitis/chemically induced
17.
Ophthalmologe ; 99(4): 289-94, 2002 Apr.
Article in German | MEDLINE | ID: mdl-12058506

ABSTRACT

BACKGROUND: To study the role of macrophages in experimental melanin-induced uveitis (EMIU), we used the method of intravital microscopy to analyse changes in leukocyte adhesion to iris venules of live rats with EMIU after pretreatment with liposomal clodronate. MATERIALS AND METHODS: EMIU was induced in Lewis rats (n = 48) by intraperitoneal immunisation with bovine crude melanosomes emulsified in complete Freund's adjuvant (CFA) and pertussis toxin (PTX). Control animals received CFA and PTX only (n = 12) or no injection (n = 6). Animals were treated with liposomal clodronate (DMDP-lip) or empty liposomes on days -2, +1, 4, 6 and 8. Using IVM, postcapillary iris venules of rats were examined to quantify leukocyte rolling and firm adhesion to the vascular endothelium. RESULTS: Depletion of macrophages caused a decreased percentage of rolling leukocytes on day 8 (2 +/- 1.1% vs 15.2 +/- 1.6%, DMDP-lip vs EMIU, mean +/- SEM, ANOVA, p < 0.05) and day 10 (2.6 +/- 0.3% vs 14.2 +/- 1.6%). A significant decline in the number of firmly adherent leukocytes was detected on days 8 and 10 (88 +/- 13/mm2 vs 175 +/- 18/mm2 and 129 +/- 13/mm2 vs 372 +/- 31/mm2, DMDP-lip vs EMIU). Treatment with empty liposomes showed no changes in leukocyte firm adhesion. CONCLUSIONS: Elimination of macrophages prevents the induction of EMIU. In autoimmune-mediated uveitis, macrophages play a crucial role in the initiation of leukocyte-endothelium interaction.


Subject(s)
Macrophages/immunology , Neutrophil Infiltration/immunology , Uveitis, Anterior/immunology , Animals , Cattle , Ciliary Body/immunology , Clodronic Acid/pharmacology , Female , Iris/immunology , Leukocyte Count , Liposomes , Melanins/immunology , Microscopy, Fluorescence , Rats , Rats, Inbred Lew
18.
Ophthalmic Res ; 33(5): 256-63, 2001.
Article in English | MEDLINE | ID: mdl-11586058

ABSTRACT

To investigate the effects of thalidomide on leukocyte-endothelium interaction in iris vessels of rats with an endotoxin-induced uveitis (EIU), intravital fluorescence microscopy was used to quantify leukocyte adhesion to the vascular endothelium of iris venules in Lewis rats at 2, 4, 8 and 24 h after induction of EIU. Animals (n = 84) received a single intraperitoneal dose of either thalidomide (80 mg/kg body weight) or prednisolone (10 mg/kg body weight). Both drugs significantly reduced firm adhesion of leukocytes at 4, 8 and 24 h. Thalidomide caused earlier suppression of leukocyte rolling than prednisolone (4 vs. 8 h). TNF-alpha plasma levels peaked at 2 h and were not significantly reduced in any group compared with controls. Cell count and protein concentration in aqueous humor were significantly reduced by prednisolone and thalidomide at 24 h (p < 0.05). Thalidomide exerts its anti-inflammatory effects by an inhibition of leukocyte-endothelium interaction. Compared with prednisolone, thalidomide shows earlier inhibition of leukocyte rolling, indicating modulation of adhesion molecule expression and/or function.


Subject(s)
Endothelium, Vascular/drug effects , Immunosuppressive Agents/pharmacology , Leukocytes/drug effects , Thalidomide/pharmacology , Uveitis, Anterior/prevention & control , Animals , Cell Adhesion/drug effects , Enzyme-Linked Immunosorbent Assay , Female , Glucocorticoids/pharmacology , Iris/blood supply , Leukocyte Count , Lipopolysaccharides , Microscopy, Fluorescence , Prednisolone/pharmacology , Rats , Rats, Inbred Lew , Salmonella typhimurium , Tumor Necrosis Factor-alpha/metabolism , Uveitis, Anterior/chemically induced
19.
Ophthalmologe ; 98(8): 731-5, 2001 Aug.
Article in German | MEDLINE | ID: mdl-11552412

ABSTRACT

BACKGROUND: RGD peptides competitively inihibit adhesion molecules of the lens epithelial cells (LEC). The purpose of our study was to investigate whether this peptide is capable of detaching adherent cells and preventing posterior capsule opacification (PCO). METHODS: Cultures of bovine and human LECs on culture dishes and discs of bovine anterior lens capsules were used. The inhibition of adhesion and the detachment of confluent LEC layers by the cyclic RGD peptide cRGDdFV were studied (incubation time was 3 days and 1 h and concentrations of 10(-4) and 10(-3) M were used). RESULTS: A dose-dependent inhibition of adhesion (48% and 42%, respectively) was obtained. There was a significant difference between the control peptide group and cRGDdFV (p < 0.0001). Cell detachment from lens capsules was not achieved but complete detachment from the culture dish occurred after 37 min. CONCLUSIONS: Short-term incubation of LECs by cRGDdFV did not lead to a sufficient inhibition of adhesion in vitro. A detachment of adherent LECs by cRGDdFV was not achieved.


Subject(s)
Cataract/prevention & control , Epithelial Cells , Lens, Crystalline/cytology , Oligopeptides/pharmacology , Adhesiveness/drug effects , Animals , Antineoplastic Agents/pharmacology , Cattle , Cells, Cultured , Epithelial Cells/drug effects , Humans , Lens, Crystalline/drug effects , Time Factors
20.
Exp Eye Res ; 73(1): 101-9, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11428867

ABSTRACT

The purpose was to study the effects of macrophage depletion with liposomal dichloromethylene-diphosphonate (Cl(2)MDP-lip) on inflammation and leukocyte-endothelium interaction in experimental melanin-protein induced uveitis (EMIU). Lewis rats (n = 48) were immunized with melanin-associated protein in complete Freund's adjuvant and pertussis toxin. Control groups received adjuvants without the antigen (n = 12) or no injection (n = 6). Animals received treatment with either CL(2)MDP-lip or empty liposomes (empty-lip) on day -2, 1, 4, 6 and 8. Leukocytes were stained with rhodamine 6G i.v. and intravital fluorescence microscopy (IVM) was performed on day 4, 6, 8 and 10 to quantify leukocyte rolling and arrest. After IVM, the cell count and protein concentration were determined in aqueous humor and plasma levels of TNF-alpha and IFN-gamma were measured by ELISA. In EMIU, leukocyte rolling increased on day 4 (10.0 +/- 1.2 cells min(-1)vs baseline of 5.7 +/- 0.7 cells min(-1), mean +/- S.E.(M.)) and peaked on day 8 (40.8 +/- 4.2 cells min(-1);P < or = 0.05). Leukocyte arrest was increased on day 8 (175.4 +/- 18.2 cells mm(-2)vs baseline of 59.7 +/- 7.1 cells mm(-2);P < or = 0.05) and day 10 (371.7 +/- 30.7 cells mm(-2)). CL(2)MDP-lip prevented leukocyte rolling (day 10: 16.6 +/- 1.8 cells min(-1)vs 30.7 +/- 2.9 cells min(-1); CL(2)MDP-lip vs untreated EMIU;P < or = 0.05) and arrest (day 8: 88.3 +/- 13 cells mm(-2); day 10: 128.5 +/- 12.9 cells mm(-2);P < or = 0.05). Empty-lip had no effect on leukocyte rolling (day 10: 34.8 +/- 4.2 cells min(-1)) or arrest (day 8: 159.3 +/- 12.9 cells mm(-2), day 10: 421.2 +/- 41.6 cells mm(-2)). CL(2)MDP-lip completely suppressed leukocyte emigration (11 +/- 2 cells microl(-1)vs 100 +/- 29 cells microl(-1); CL(2)MDP-lip vs empty-lip;P < or = 0.05) and protein extravasation into aqueous humor (2.7 +/- 0.3 mg ml(-1)vs 14.2 +/- 2.1 mg ml(-1); CL(2)MDP-lip vs empty-lip;P < or = 0.05), abrogated the TNF-alpha response (32.5 +/- 2.7 pg ml(-1)vs 954.9 +/- 216.3 pg ml(-1); CL(2)MDP-lip vs untreated EMIU;P < or = 0.05) and caused an attenuated and delayed elevation of IFN-gamma. CL(2)MDP-lip prevented the inflammatory reaction of EMIU and inhibited the increase of leukocyte-endothelium interaction in iris vessels. Our findings emphasize the pivotal role macrophages play in the initiation of autoimmune disease.


Subject(s)
Autoimmune Diseases/immunology , Leukocytes/physiology , Macrophages/physiology , Uveitis/immunology , Analysis of Variance , Animals , Aqueous Humor/chemistry , Cell Adhesion/physiology , Cell Count , Cell Migration Inhibition , Clodronic Acid/pharmacology , Endothelium, Vascular/immunology , Enzyme-Linked Immunosorbent Assay , Female , Image Processing, Computer-Assisted , Interferon-gamma/blood , Microscopy, Fluorescence , Rats , Rats, Inbred Lew , Statistics, Nonparametric , Tumor Necrosis Factor-alpha/analysis
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