Inflammatory Corneal Diseases Research Articles

Inflammatory profile of keratoconic corneal epithelium

BackgroundRecent studies have presented inflammatory features on keratoconus (KC) and many inflammatory markers are described in the tears of patients with this disease. The KC pathogenesis is still unknown just like the correlation with inflammatory patterns. However, environmental and genetic issues may be part of the progress of KC. In addition, some systemic features, such as allergy and obesity, seem to be related to the progression of KC. Our purpose was to evaluate the neuropeptides vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), chemokines ligand 2 (CCL-2) and 5 (CCL-5), and interleukins 6 (IL-6) and 8 (IL-8) on corneal epithelial cells and blood of patients with KC and in healthy controls. In addition, the neutrophil-to-lymphocyte ratio (NLR) was evaluated to predict inflammation.MethodsThis including prospective observational study included 32 KC patients who underwent corneal crosslinking (CXL) and 32 control patients who underwent photorefractive keratectomy (PRK). Patients’ corneal epithelial cells were removed surgically, and blood (buffy coat) was analyzed. Samples in triplicate were evaluated on rt-PCR for neuropeptides (VIP e NPY), interleukins (IL-6 e IL-8), and chemokines (CCL-2 and CCL-5).ResultsOur study showed statistically higher CCL-5 and IL-8 on corneal epithelial cells in patients with KC. Blood cells were statistically higher in VIP and NPY in the KC group. Interleukin-8 on blood cells was statistically significant in KC’S group; for CCL-2 and CCL-5 they were statistically lower in patients with KC compared with controls. NLR showed no difference between the groups.ConclusionsOur data support the findings of other studies that suggested altering KC status, such as inflammatory corneal disease. The presence of IL-8 in the cornea and blood samples of KC’s group suggested systemic disease with a possible local or repercussion action. Further studies are warranted to elucidate KC pathogenesis and its correlation to systemic disease.

Comparative Analysis of Deep Learning Methods for Detection of Keratoconus

Keratoconus eye disease is not an inflammatory corneal disease that is caused by progress in thinning of the cornea, scarring, and deformation in the shape of the cornea. In India, there is a significant increase in the number of cases of keratoconus, and several research centers have been paying attention to this disease in recent years. In this situation, there is an immediate need for tools that simplify both diagnosis and treatment[1]. The algorithm developed can decide whether the eye is a normal eye or keratoconus eye with stages. The K-net model analyzes the pentagram images of the eye using a convolutional neural network(CNN) a deep learning model and pre-trained ResNet-50 and InceptionV3 pre-trained models and does the comparative analysis of the accuracies of these models. The results show that the Keratoconus Detection algorithm leads to a good job, with a 93.75 percent accuracy on the data test collection. Keratoconus Detection model is a program that can help ophthalmologists test their patients faster, therefore reducing diagnostic errors and facilitating treatment.

An approach to inflammatory corneal diseases—the role of contemporary methods

An approach to inflammatory corneal diseases—the role of contemporary methods

Is Keratoconus an Inflammatory Disease? The Implication of Inflammatory Pathways

ABSTRACT Purpose Keratoconus is considered a non-inflammatory condition. Recently however, increased proinflammatory cytokines have been detected in the tears of keratoconic patients and clinical and immunohistochemical observations reported infiltration of matured dendritic cells and leukocytes. Our laboratory utilized cytokine antibody arrays to elucidate the inflammatory aspects of keratoconus. Methods Protein was extracted from 42 corneal buttons (14 keratoconic and 28 non-keratoconic) and incubated with cytokine antibody arrays scanning 120 cytokines. Mann Whitney U test with a p-value of <0.05 was considered significant. Results Pathways for wound healing, neuroprotection, angiogenesis, and inflammation were activated in keratoconic samples with 23 cytokines showing significant elevation. Fifteen were expressed only in keratoconus with 8 cytokines elevated 1.7–42-fold. Conclusion This study identified elevated inflammatory pathways covering immune responses in keratoconus. Our results support the evidence for inflammatory pathway activation in keratoconus and a possible redefinition of keratoconus as a chronic inflammatory corneal disease.

Effect of Tempol, a Membrane-Permeable Free Radical Scavenger, on In Vitro Model of Eye Inflammation on Rabbit Corneal Cells.

Purpose: Inflammatory corneal diseases such as bacterial keratitis provoke severe injury to the visual functions and physical structure, leading to opaqueness, wounding, damage to the cornea, and even long-lasting vision loss. Usually antioxidant substances have been of great attention as candidate therapies in the management of keratitis in both humans and animals. Based on the findings, the aim of our research was to examine the effects of Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a membrane-permeable free radical scavenger with exclusive antioxidant properties, on in vitro model of eye inflammation of rabbit corneal cells stimulated with lipopolysaccharide (LPS) (Seruminstitute Rabbit Cornea). Methods: The cells were pretreated with Tempol and incubated with LPS for 24 h. LPS stimulation triggered increased cellular mortality, oxidative stress, cytokine levels expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, and also enhanced prostaglandin E2 (PGE2) levels and cyclooxygenase-2 (COX-2) expression. Results: Pretreatment with Tempol (3 mM) significantly increased cell viability and antioxidant activity as well as decreased reactive oxygen species production, cytokines, PGE2 levels, and COX-2 expression. Conclusions: Taken together, Tempol could be a new therapeutic strategy for management of ocular inflammatory disorders for clinical and veterinary use.

NLRP3, NLRP12, and IFI16 Inflammasomes Induction and Caspase-1 Activation Triggered by Virulent HSV-1 Strains Are Associated With Severe Corneal Inflammatory Herpetic Disease.

The crosstalk between the host's inflammasome system and the invading virulent/less-virulent viruses determines the outcome of the ensuing inflammatory response. An appropriate activation of inflammasomes triggers antiviral inflammatory responses that clear the virus and heal the inflamed tissue. However, an aberrant activation of inflammasomes can result in a harmful and overwhelming inflammation that could damage the infected tissue. The underlying host's immune mechanisms and the viral virulent factors that impact severe clinical inflammatory disease remain to be fully elucidated. In this study, we used herpes simplex virus type 1 (HSV-1), the causative agent of corneal inflammatory herpetic disease, as a model pathogen to determine: (i) Whether and how the virulence of a virus affects the type and the activation level of the inflammasomes; and (ii) How triggering specific inflammasomes translates into protective or damaging inflammatory response. We showed that, in contrast to the less-virulent HSV-1 strains (RE, F, KOS, and KOS63), corneal infection of B6 mice with the virulent HSV-1 strains (McKrae, 17 or KOS79): (i) Induced simultaneous expression of the NLRP3, NLRP12, and IFI16 inflammasomes; (ii) Increased production of the biologically active Caspase-1 and pro-inflammatory cytokines IL-1β and IL-18; (iii) Heightened recruitment into the inflamed cornea of CD45highLy6C+Ly6G−F4/80+CD11b+CD11c− inflammatory monocytes and CD45highCD11b+F4/80−Ly6GhiLy6Cmed neutrophils; and (iv) This intensified inflammatory response was associated with a severe corneal herpetic disease, irrespective of the level of virus replication in the cornea. Similarly, in vitro infection of human corneal epithelial cells and human monocytic THP-1 cells with the virulent HSV-1 strains triggered a synchronized early expression of NLRP3, NLRP12 and IFI16, 2 h post-infection, associated with formation of single and dense specks of the adapter molecule ASC in HSV(+) cells, but not in the neighboring bystander HSV(−) cells. This was associated with increased cleavages of Caspase-1, IL-1β, and IL-18. These findings suggest a previously unappreciated role of viral virulence in a synchronized early induction of the NLRP3, NLRP12, and IFI16 inflammasomes that lead to a damaging inflammatory response. A potential role of common virus virulent factors that stimulate this harmful inflammatory corneal disease is currently under investigation.

The Role of Connexin-43 in the Inflammatory Process: A New Potential Therapy to Influence Keratitis.

The studies outlined in this review highlight the relationship between inflammatory signaling molecules and connexin-43 (Cx43). Gap junction (GJ) channels and hemichannels (HCs) participate in the metabolic activity between intra- and extracellular space. Some ions and small molecules are exchanged from cell to cell or cell to extracellular space to affect the process of inflammation via GJ. We analyzed the effects of signaling molecules, such as innate immunity messengers, transcription factors, LPS, cytokine, inflammatory chemokines, and MMPs, on Cx43 expression during the inflammatory process. At the same time, we found that these signaling molecules play a critical role in the pathogenesis of keratitis. Thus, we assessed the function of Cx43 during inflammatory corneal disease. Corneal healing plays an essential role in the late stage of keratitis. We found that Cx43 is involved in wound healing. Studies have shown that the decrease of Cx43 can decrease the time of healing. We also report several Cx43 mimic peptides which can inhibit the activity of Cx43 Hc to mediate the releasing of adenosine triphosphate (ATP), which may in turn influence the inflammatory process.

Osteo-odonto keratoprosthesis: Innovative dental and ophthalmic blending.

Corneal diseases are among the major causes of global blindness, secondary to cataract. osteo-odonto keratoprosthesis (OOKP) is the ideal treatment for patients with end-stage inflammatory corneal diseases where a portion of tooth along with bone is used to support an optical cylinder to restore vision in such patients. OOKP surgery requires multidisciplinary approach involving dentists, ophthalmologists, and radiologists. Very less is known in dentistry about the role of the periodontium in the field of ophthalmology. This paper highlights OOKP indications, contraindications, surgical procedure, role of oral structures, advantages, and limitations.

Paraproteinemic Keratopathy as a Clinical Sign of Monoclonal Gammopathy

Patients with monoclonal gammopathy can show paraproteinemic keratopathy (PPK) with an indication to treatment. PPK has to be differentiated from corneal dystrophies, systemic metabolic disorders with corneal involvement, as well as from immunologic and inflammatory corneal diseases.

Bacterial Keratitis

Worldwide inflammatory corneal diseases are considered to be one of the leading causes of monocular blindness. Bacterial infectious are still predominant and are found in 80 % of patients with ulcerative keratitis. In recent years, both changes in risk conditions and changes in the bacterial spectrum can be observed. Contact lenses and refractive surgery are factors that have increased in importance according to some studies. Microorganisms especially Pseudomonas spp. and atypical mycobacteria are detectable in these patients. In contrast, the bacterial keratitis is observed less frequently after trauma. The broad, often unsighted use of highly effective antimicrobial agents, especially of fluoroquinolones is assumed to be a factor in the transformation of the microbial spectrum. Due to the frequent course of keratitis and a targeted, effective therapy to initiate a pathogen is desirable. The possibilities of diagnostics have been expanded in recent years by molecular biological techniques, but cannot replace established methods. The aim of this paper is to provide a positioning on current aspects of bacterial keratitis.

Significance of arachidonic acid in ocular infections and inflammation.

Innate immune responses in the cornea mainly play an important role to mobilize multiple interrelated pathways of corneal lipid, which involve in inflammatory corneal diseases. Signaling lipid mediators derived from arachidonic acid (AA) control cell proliferation, apoptosis, metabolism, and migration, are known as eicosanoids, phosphoinositides, sphingolipids, and fatty acids. Emerging evidences have highlighted the implication of lipid mediators in both injury and repair mechanisms in the cornea. Recently, the role of AA and its metabolites to induce proinflammatory mediators and inflammatory cell infiltration in the pathogen-infected cornea and to cause severe keratitis have been revealed. In this review, we focus on the novel roles of AA downstream signaling in the corneal inflammatory diseases and also the biological relevance of AA signaling in the therapeutic strategies for targeting sight-threatening diseases.

Self-Assembling Colloidal System for the Ocular Administration of Cyclosporine A

In this study, we developed a self-assembling micellar system to deliver cyclosporine A (CsA) in an aqueous solution to the cornea. Two nonionic surfactants of the poly(ethylene glycol)-fatty alcohol ether type (Sympatens AS and Sympatens ACS) were characterized in terms of micelle size, shape, and charge, and their encapsulation efficiency for CsA. In an in situ single dose bioavailability study, the corneal CsA levels were determined in an enucleated porcine eye model. A commercial formulation and a 2% CsA olive oil solution served as references. Both surfactants formed spherical micelles with a size of 9 to 12 nm in water. A concentration as low as 0.3% (wt/vol) Sympatens AS was sufficient to entrap therapeutic levels of at least 0.1% (wt/vol) CsA. In the porcine in situ model, exceptionally high drug levels in the cornea were obtained for the micellar CsA solution (1557 ± 407 ngCsA/gcornea). They were significantly higher than those of Restasis (545 ± 137 ngCsA/gcornea) or the olive oil solution (452 ± 142 ngCsA/gcornea). In conclusion, we have shown a promising simple and efficient approach for the application of CsA in an aqueous solution to the cornea to treat inflammatory corneal diseases.

A study of the association between chronic superficial keratitis and polymorphisms in the upstream regulatory regions of DLA-DRB1, DLA-DQB1 and DLA-DQA1

Canine chronic superficial keratitis (CSK) is an inflammatory corneal disease that primarily occurs in German shepherd dogs (GSDs). Several studies support the hypothesis that CSK is an immune-mediated disease. To investigate the genetic factors associated with CSK development, the upstream regulatory regions (URRs) of the DLA-DRB, -DQA and -DQB genes were genotyped in 60 dogs, including 32 CSK animals. LD analysis identified two blocks (r2≤45), with two DLA-DRB1 and five DLA-DQB1 haplotypes. Analysis of DLA-URR alleles/haplotypes showed a significant association between DQB1*-154 [C/T] (p=0.016) and CSK, suggesting that the T variant may increase the risk for developing CSK disease (OR=3, 95% CI=1.25–7.68). When haplotype associations were performed, the URR-DQB*CATT haplotype was significantly associated with CSK (p=0.016), increasing the risk of develop this disease over two-fold (OR=3, 95%, CI=1.25–7.68). These results showed that dogs homozygous at DRB1*69 [C/T] had a risk for developing CSK disease that was over four times the risk for heterozygotes. This genetic association supports the previous clinical, histological and pharmacological studies that suggest that CSK is an immune-mediated disease, and this association could potentially be used to identify susceptible animals.

Ocular delivery systems for poorly soluble drugs: An in-vivo evaluation

For highly potent but poorly water-soluble drugs like cyclosporine A, the development of aqueous formulations providing an increase of corneal drug tissue levels, and thus of bioavailability, to increase patient compliance is still a challenge. Therefore, we designed two water-based liquid application systems, an in-situ nanosuspension (INS) and a micellar solution (MS), and tested both formulations in vivo at the rabbit cornea for tolerability and the tissue uptake of CsA. The evaluation of the biological tolerability by periodical eye examination during 180 min and quantification in a defined grading system revealed that the INS evoked minimal to no irritations whereas the MS was perfectly tolerated. After the observation period, the rabbits were sacrificed and the corneal tissue levels of CsA were analyzed. The INS and the MS both showed high levels of 1683±430 ngCsA/gcornea and 826±163 ngCsA/gcornea, respectively, and exceeded drug tissue levels reported for Restasis(®) (350 ngCsA/gcornea) and cationic emulsions (750 ngCsA/gcornea). These results marked our INS and MS as outstanding novel approaches for the treatment of inflammatory corneal diseases.

Distribution of Antigen Presenting Cells in the Human Cornea: Correlation of In Vivo Confocal Microscopy and Immunohistochemistry in Different Pathologic Entities

Purpose: The purpose of this study was to determine the quantity and distribution of antigen presenting cells (APC) in various inflammatory and non-inflammatory corneal diseases, comparing in vivo confocal microscopy (IVCM) and immunohistochemistry.Material and methods: Corneae of 41 eyes, composed of group 1 (status post herpes-keratitis), group 2 (keratoconus) and group 3 (graft rejection after keratoplasty) were investigated. IVCM was used preoperatively to assess the distribution and density of dendritic cells in the corneal center versus the paracentral area. Afterwards, all patients underwent penetrating keratoplasty. The host corneas were analyzed by immunohistochemistry for antigen presenting cell distribution, density and characterization by using specific markers for CD207/Langerin, CD209/DC-SIGN and HLA-DR. The IVCM findings were compared with immunohistochemistry results in the corneal epithelium.Results: Cells with branching dendritic morphology were visualized by IVCM mainly in the basal epithelial layer and subepithelial nerve plexus of the central and paracentral cornea. The density of APC in IVCM decreased in all groups towards the central part of the cornea. The highest gradient was observed in group 2, followed by groups 1 and 3. The corneal paracenter showed similiar distribution of APC in group 1 and 2 (76.7 cells/mm2 and 74.4 cells/mm2). The highest density of central APC was observed in group 1 (53.76 cells/mm2), followed by group 3 (27.0 cells/mm2) and group 2 (24.2 cells/mm2). In immunohistochemistry positive stained, APC were distributed similarly to IVCM but with a higher density (p < 0.05).Conclusion: Distribution, density and stage of maturation of corneal epithelial APCs can be evaluated on morphological basis by IVCM. However, the corneal APCs density was about three-fold lower compared to immunohistochemistry findings.

Inhibitory effects of eicosapentaenoic acid on expression of nuclear factor-kB and cytokine in rat corneal neovascularization

Background Corneal neovascularization (CNV) is an important cause of visual impairment and graft rejection after allograft corneal transplantation in inflammatory corneal diseases. The mechanisms and therapy relating to CNV are intensely investigated at all times. Objective This study was to evaluate the effect of eicosapentaenoic acid (EPA) on CNV induced by alkali cauterization and its mechanism. Methods The animal models of corneal neovasculation were induced in the right eyes in 72 Sprayue-Dawley rats by putting a piece of 3 mmfilter paper with 1 mol/L NaOH at the center of the cornea for 30 seconds. The rats were then divided randomly into the 0.02 mg EPA treatment group (24 rats) ,0.03 mg EPA treatment group (24 rats) ,model group (24 rats) and normal group (6 rats). EPA of 0.04 ml with doses of 0.02 mg or 0. 03 mg or saline solution of 0. 04 ml was injected subconjunctivally in model rats and immediately after cauterization. The presence of CNV and corneal edema were observed daily by slit lamp biomicroscope. 1,4,7 and 14 days after operation, corneal histopathological examination was performed by hematoxylin and eosin staining. The vascular endothelial cells were stained with CD34 by immunohistochemistry,and the expression of IL-1α,IL-6 mRNA and the nuclear factor-κBp65 ( NF-κBp65 ) proteins was measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The use of animals complied with the Regulations for the Administration of Affair Concerning Experimental Animals by Hebei Province( version 1998 ). Results Under the slit lamp, CNV grew slowly from days 2-4 with obvious corneal edema and defect of epithelium. Larger CNV area and less edema were seen from days 7-10. Maximal vessel growth was observed 14 days after injury with thinner vessels in the model group. Histological examination showed that part of the corneal epithelium was damaged;serious corneal edema, more inflammatory cells and a lot of CNV in the stroma were presented in the model group. However, repairing of the corneal epithelium without CNV ,light corneal edema and less inflammatory cells were found in both the 0. 02 mg EPA and 0. 03 mg EPA treatment groups 7 days after alkali cauterization. The relative area of CNV in the 0. 02 mg EPA treatment group was ( 15.80±6.43 )% and ( 11.06±2. 14)% ,and that in the 0. 03 mg EPA treatment group was (16. 10±7.41 )% and (11.06±2. 51 )%, showing significant reduction in comparison with the model group [ (84. 74±7.77)% and (89.63±7.50) % ] 7 days and 14 days after operation ( P＜0. 05 ). Stronger expression of CD34 in the vascular endothelial cells of the cornea stroma was observed in the model group and an absence of CD34 was observed in the EPA-treated groups on the 7th day. RT-PCR revealed that the expression of IL-1α mRNA and IL-6 mRNA was lower in the EPA treatment groups than the model group ( P＜0. 05 ), and Western blot analysis showed that the expression of NF-κB/p65 in the corneas in the EPA treatment groups was significantly lower than that in the model group on the 4th day after operation (P＜0.05).Conclusion Topical application of EPA suppresses CNV induced by alkali burn possibly by inhibiting the expression of NF-κB,IL-1α and IL-6. Key words: Corneal neovascularization; Eicosapentaenoic acid; Interleukin-1α; Interleukin-6; Nuclear factor kappa B

Using synergistic effects in targeting angiogenesis: combination therapy for corneal neovascularization

Evaluation of: You IC, Im SK, Lee SH, Yoon KC. Photodynamic therapy with verteporfin combined with subconjunctival injection of bevacizumab for corneal neovascularization. Cornea 30(1), 30–33 (2011).Corneal neovascularization occurs following infectious, ischemic, inflammatory and other corneal diseases, as well as corneal injuries. It has a detrimental effect on visual acuity and also presents a significant risk for the failure of corneal grafting. To date, the therapeutic modalities are limited and address either the underlying inflammatory and infectious processes or selectively ablate those vessels using photocoagulation or diathermy. More recent strategies include pharmacological inhibition of various steps of angiogenesis and selective photochemical vascular occlusion with photodynamic therapy. The article under evaluation presents a prospective, interventional case series treating corneal neovascularization with a combination of photodynamic therapy and subconjunctival injection of bevacizumab (Avastin™, Genentech Inc., CA, USA). The authors reported success with complete occlusion of vessels in 66.7% of patients at 1 year following a single-session treatment. As with the success seen in treating choroidal neovascularization, this combined approach may offer more effective control and better clinical outcomes. However, further randomized trials are necessary in order to determine optimal dosing, timing as well as the potential local side effects.

In Vivo Imaging of Corneal Inflammation: New Tools for Clinical Practice and Research

Purpose: Infectious and inflammatory corneal diseases are a major cause of blindness. To date, assessment of corneal inflammation, has only been possible by slit-lamp biomicroscopy. The purpose of this study is to review the current state of imaging technologies enabling in vivo imaging of inflammation in the cornea. Methods: Literature review of peer-reviewed articles on in vivo imaging modalities. Results: Current means of diagnosis and treatment follow-up for immune and infectious keratitis are limited to slit-lamp biomicroscopy. Several modalities are currently emerging, allowing for in vivo imaging of corneal inflammation, including in vivo confocal microscopy, anterior segment optical coherence tomography, and intravital multiphoton microscopy. Conclusion: Several in vivo imaging technologies are currently evolving, allowing for objective assessment of corneal inflammation and treatment response.

Lokales Fk506 bei entzündlichen Erkrankungen von Hornhaut und Bindehaut - Eine Pilotstudie -

Hintergrund: Für eine lokale Immunmodulation gravierender entzündlicher Erkrankungen von Hornhaut und Bindehaut stehen als zugelassene Medikamente bislang nur Kortikosteroide zur Verfügung. Beachtliche Ergebnisse konnten in der Vergangenheit zwar mit lokalem Cyclosporin A erreicht werden. Es wirkt aber bei weitem nicht bei allen Patienten. Der Wirkmechanismus von Fk506 beruht wie der von Cyclosporin A in erster Linie auf der Inhibition der Transkription von Interleukin-2 in T-Lymphozyten. Es hat aber ein größeres immunsuppressives Potenzial und zudem deutlich bessere Penetrationseigenschaften. Deshalb sollte in einer klinischen Pilotstudie geprüft werden, ob sich dies theoretisch bessere therapeutische Potenzial in der klinischen Praxis wiederfinden lässt. Hierzu wurden Patienten ausgewählt, die refraktär gegenüber konventioneller Therapie waren und somit eine besondere therapeutische Herausforderung bedeuteten. Patienten und Methoden: Fk506 0,06 % wurde initial dreimal täglich bei 15 Patienten mit atopischer Blepharokeratokonjunktivitis, Ulcus Mooren, okulärem Pemphigoid, Keratitis superficialis punctata Thygeson, Nummuli nach Keratoconjunctivitis epidemica, Graft-versus-host-Reaktion der Bindehaut und Steroid-Response-Glaukom nach perforierender Keratoplastik getropft, und danach individuell ausgeschlichen. Ergebnisse: Innerhalb einer Nachbeobachtungszeit von bislang 26 ± 15 Wochen konnte bei 5/15 Patienten eine Verbesserung und bei 5/15 Patienten eine Stabilisierung erreicht werden. Lediglich bei zwei Patienten kam es zu einer Verschlechterung (einmal Progression eines okulären Pemphigoids, einmal Verdacht auf Automutilation). Bei drei Patienten wurde die lokale Fk506-Therapie frühzeitig wegen Nebenwirkungen (Oberflächenirritation) oder Complianceproblemen abgebrochen. Schlussfolgerungen: Lokales Fk506 hat offenbar besonders bei atopischer Keratokonjunktivitis, bei Keratitis superficialis punctata Thygeson und bei Keratitis nummularis ein beachtliches therapeutisches Potenzial. Wie gut es bei diesen und anderen entzündlichen Hornhaut-/Bindehauterkrankungen genau wirkt, muss in den nächsten Jahren mittels randomisierter Studien herausgearbeitet werden. Bevor diese beginnen, sollten aber die bislang zum Teil bestehenden lokalen Nebenwirkungen weiter reduziert werden.

Adhesion molecules in normal and pathological corneas. An immunohistochemical study using monoclonal antibodies.

Adhesion molecules are cell surface receptors that are probably important in various cell-cell and cell-extracellular matrix interactions of the cornea. In this immunohistochemical light-microscopic study we analyzed the expression pattern of adhesion molecules in normal and pathological human corneas (cases of corneal inflammation and degenerative disorders). The analyzed molecules included the beta 1 integrin or VLA family VLA-1-6, the beta 2 integrins or leukocyte integrins LFA-1, Mac-1, and p150,95, the immunoglobulins LFA-3, CD2, ICAM-1 and VCAM-1 and the selectins ELAM-1 and GMP-140. Inflamed cornea (in contrast to normal cornea). On corneal epithelium, increased expression of the alpha 2 subunit of VLA-2 was detected and ICAM-1 was induced on the basal epithelial cells. On corneal stromal keratocytes, LFA-3 was induced and expression of the alpha subunits of VLA-1-6 and ICAM-1 was increased. On vascular endothelium, VCAM-1 and ELAM-1 were induced and ICAM-1 and GMP-140 expression was increased. On corneal endothelium, ELAM-1 was induced and increased levels of the alpha 1 subunit of VLA-1 and GMP-140 were expressed. Degenerative disorders (in contrast to normal cornea): In corneas with degenerative disorders we found decreased expression of adhesion molecules. Inflammatory cytokines increase the expression of the adhesion molecules. Increased expression of the VLAs probably promotes cell-extracellular matrix and cell-cell interactions. ICAM-1, VCAM-1, LFA-3, ELAM-1 and GMP-140 expression was increased on vascular endothelium in inflamed corneas. Corresponding receptors on leukocytes probably enable a selective recruitment of different leukocyte populations in inflammatory corneal diseases. The decreased expression of adhesion molecules in corneal degenerative disorders is probably a sign of reduced cell-cell and cell-extracellular matrix interactions.