The Relative Importance of Topography and RGD Ligand Density for Endothelial Cell Adhesion

The morphology and function of endothelial cells depends on the physical and chemical characteristics of the extracellular environment. Here, we designed silicon surfaces on which topographical features and surface densities of the integrin binding peptide arginine-glycine-aspartic acid (RGD) could be independently controlled. We used these surfaces to investigate the relative importance of the surface chemistry of ligand presentation versus surface topography in endothelial cell adhesion. We compared cell adhesion, spreading and migration on surfaces with nano- to micro-scaled pyramids and average densities of 6×102–6×1011 RGD/mm2. We found that fewer cells adhered onto rough than flat surfaces and that the optimal average RGD density for cell adhesion was 6×105 RGD/mm2 on flat surfaces and substrata with nano-scaled roughness. Only on surfaces with micro-scaled pyramids did the topography hinder cell migration and a lower average RGD density was optimal for adhesion. In contrast, cell spreading was greatest on surfaces with 6×108 RGD/mm2 irrespectively of presence of feature and their size. In summary, our data suggest that the size of pyramids predominately control the number of endothelial cells that adhere to the substratum but the average RGD density governs the degree of cell spreading and length of focal adhesion within adherent cells. The data points towards a two-step model of cell adhesion: the initial contact of cells with a substratum may be guided by the topography while the engagement of cell surface receptors is predominately controlled by the surface chemistry

Synthesising Corporate Responsibility on Organisational and Societal Levels of Analysis: An Integrative Perspective

This article develops an integrative perspective on corporate responsibility by synthesising competing perspectives on the responsibility of the corporation at the organisational and societal levels of analysis. We review three major corporate responsibility perspectives, which we refer to as economic, critical, and politico-ethical. We analyse the major potential uses and pitfalls of the perspectives, and integrate the debate on these two levels. Our synthesis concludes that when a society has a robust division of moral labour in place, the responsibility of a corporation may be economic (as suggested under the economic perspective) without jeopardising democracy and sustainability (as reported under the critical perspective). Moreover, the economic role of corporations neither signifies the absence of deliberative democratic mechanisms nor business practices extending beyond compliance (as called for under the politico-ethical perspective). The study underscores the value of integrating different perspectives and multiple levels of analysis to present comprehensive descriptions and prescriptions of the responsibility phenomenon

Topical use of Cyclosporine in the treatment of vernal keratoconjunctivitis.

I.F. 1.82

Serpiginous Choroiditis does not always progress within previously hypoperfused areas of choroid

Purpose: Recent clinical reports claim that progression of serpiginous choroiditis, and of other inflammatory diseases developing at the outer retina/ choriocapillary interfacies, takes always (or most often) place within areas of previous choroidal hypoperfusion. We have used Indocyanine green (ICG) choroidal angiography in longitudinal studies, in order to find out whether this is always the case. Methods. A cohort of 12 patients affected by progressive serpiginous choroiditis is currently being followed up in our Uveitis Clinic. Monitoring of the diseese's progression in each petient includes ICG choroidal angiography, repeated at least twice per year, or more often when the disease shows fast progression. Results. While in some cases the diseasewas seen, to progress within areas of previous chronic choroidal hypoperfusion, in other cases (or, in the same patient, in different areas of progression) the disease was seen to advance in healthy areas of choroid - previously (10-20 days before clinical changes) shown normally perfused by ICG observation - while sparing chronically hypoperfused areas. Conclusions. Choroidal hypoperfusion does neither represent in all instances a prerequisite for progression of serpiginous choroidtis, nor a clear warning for impending advancement of the disease. None

Tear eosinophil cationic protein (ECP) in tears of normal subjects and patients affected by vernal keratoconjunctivitis.

I.F. 5.99

Th1- and Th2-type cytokines in chronic ocular allergy

BACKGROUND: Previous reports have suggested that Th2-type cytokines are important in the pathogenesis of ocular allergic diseases. The purpose of this study is to measure levels and mRNA expression of Th1- and Th2-type cytokines in patients with active vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). METHODS: Tear samples and tear-isolated cells were obtained from 9 healthy participants (CT--controls), 28 VKC, and 6 AKC patients. IL-4, IL-13, and interferon gamma (IFNgamma) tear levels were determined by ELISA, and IL-4 and IFNgamma tear cell mRNA expression by RT-PCR. Effects of these cytokines on IL-6 and IL-8 secretion, and on ICAM-1 expression by conjunctival fibroblasts, were evaluated by ELISA and flow cytometry respectively. RESULTS: Interleukin-4 tear levels were increased in VKC and AKC compared with CT, but only IFNgamma significantly correlated with corneal involvement. An IL-4/13-dominant profile was found in 50% of VKC and in 17% of AKC patients, while a IFNgamma-dominant profile was found in 18% of VKC and in 17% of AKC patients. IL-4 and IFNgamma transcripts were detected in tear cells from 11 out of 12 VKC patients. IFNgamma upregulated expression of ICAM-1 on conjunctival fibroblasts and the secretion of IL-6 and IL-8. CONCLUSIONS: Although both IL-4 and IFNgamma are detected in tears, only IFNgamma levels correlated with disease severity and upregulated ICAM-1 on conjunctival fibroblasts, suggesting the role of IFNgamma in the inflammatory phase of chronic allergic eye diseases

Procollagens and inflammatory cytokine concentrations in tarsal and limbal vernal keratoconjunctivitis.

o quantify the presence of inflammatory/fibrogenic cytokines and procollagens type I (PICP) and III (PIIIP) in active and non-active tarsal and limbal forms of vernal keratoconjunctivitis (VKC), tear and blood samples were collected from 27 VKC patients (20 active and 7 non-active) and 15 normal subjects. Upper tarsal conjunctival biopses were obtained from 8 controls and 8 tarsal VKC patients. From biopses of 4 tarsal VKC, fibroblasts were cultured in F12 medium with 10% FCS. TGF-beta 1, IL-1 alpha, IL-1 beta, IL-6 and TNF-alpha, PICP and PIIIP were measured in: (1) tears, (2) homogenized conjunctival tissues, (3) serum, (4) supernatants of tissue cultures at 24 hr, and fibroblast primary passage cultures. Results showed: (1) in tears, TGF-beta 1 and TNF were identified in several active VKC patients without significant differences between the tarsal and the limbal forms. IL-1 beta (27 +/- 51 pg ml-1, P = 0.03) and IL-6 (28 +/- 43 pg ml-1, P = 0.006) were significantly increased in tarsal VKC compared to controls. Both control and non-active VKC tear samples had undetectable levels of all of the above cytokines. PICP and PIIIP were significantly increased in tarsal VKC compared to both limbal VKC and controls. Non-active VKC levels were similar to controls. (2) In homogenized VKC tissues, TGF-beta 1 and IL-6 were both significantly increased compared to controls (P < 0.01) while no increases were observed in IL-1 and TNF-alpha. (3) In serum, IL-1 alpha, IL-1 beta and TNF-alpha were higher in VKC patients compared to controls. (4) In vitro fibroblasts from VKC patients showed an increased production of TGF-beta 1, IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, PICP, and PIIIP over time. Increased levels of TGF-beta 1, IL-1 and IL-6 in VKC tissues and tears indicate a local production of these cytokines in active VKC. Collagen hyperproduction occurs only in active tarsal VKC and may be related to high levels of TGF-beta 1, IL-1 and IL-6. Increased serum levels of IL-1 and TNF-alpha suggests that systemic immunological changes occur in VKC. Cell culture can be used as a model to further study the pathogenesis of VKC and its characteristic local fibroblast activation

Effect of lodoxamide and disodium cromoglycate on tear eosinophil cationic protein in vernal keratoconjunctivitis.

AIM: To validate the use of tear eosinophil cationic protein (ECP) as a marker for eosinophil activation, and its pharmacological modulation, in addition to evaluating the efficacy of lodoxamide and sodium cromoglycate in the treatment of vernal keratoconjunctivitis (VKC). METHODS: Tears were collected from 30 patients affected by active mild to moderate VKC before and after therapy with disodium cromoglycate 4% (DSCG) (n = 15) or lodoxamide 0.1% (n = 15) for 10 days. Tear cytology and ECP measurement were performed, and ocular signs and symptoms evaluated. RESULTS: While statistically significant changes did not occur after DSCG therapy, mean tear ECP increased from 343 (SD 363) micrograms/l to 571 (777) micrograms/l due to marked elevation in six eyes. The clinical score in DSCG eyes did not improve. After lodoxamide therapy, both clinical signs and symptoms, and tear ECP levels (560 (756) micrograms/l to 241 (376) micrograms/l) decreased significantly (p < 0.0001 and p < 0.01, respectively). Compared with DSCG treatment, lodoxamide was more effective in reducing signs and symptoms (p < 0.005). ECP levels were significantly correlated with signs, symptoms, corneal involvement, and number of eosinophils in tears (p < 0.0001). CONCLUSIONS: In patients with VKC, lodoxamide significantly reduced ECP tear levels, and thus, eosinophil activation, and was more effective than DSCG in reducing clinical signs and symptoms