Dendritic cells in the cornea during Herpes simplex viral infection and inflammation.

Herpes simplex keratitis is commonly caused by Herpes simplex virus type 1, which primarily infects eyelids, corneas, or conjunctiva. Herpes simplex virus type 1-through sophisticated interactions with dendritic cells (DCs), a type of antigen-presenting cell)-initiates proinflammatory responses in the cornea. Corneas were once thought to be an immune-privileged region; however, with the recent discovery of DCs that reside in the cornea, this long-held conjecture has been overturned. Therefore, evaluating the clinical, preclinical, and cell-based studies that investigate the roles of DCs in corneas infected with Herpes simplex virus is critical. With in vivo confocal microscopy, animal models, and cell culture experiments, we may further the understanding of the sophisticated interactions of Herpes simplex virus with DCs in the cornea and the molecular mechanism associated with it. It has been shown that specific differentiation of DCs using immunohistochemistry, flow cytometry, and polymerase chain reaction analysis in both human and mice tissues and viral tissue infections are integral to increasing understanding. As for in vivo confocal microscopy, it holds promise as it is the least invasive and a real-time investigation. These tools will facilitate the discovery of various targets to develop new treatments.

An Immunohistochemical Study of Inflammatory Cell Changes and Matrix Remodeling With and Without Acute Hydrops in Keratoconus.

PURPOSE: To determine the inflammatory cell and matrix changes in advanced keratoconus, including acute hydrops, using immunohistochemical analysis. METHODS: The corneal tissue from eight subjects with keratoconus undergoing corneal transplantation (three keratoconic buttons, five buttons post acute hydrops­one of them with extensive neovascularization following hydrops) was compared with tissue from two normal corneoscleral rims (n = 10). The corneas were sectioned and analyzed with specific markers for macrophages, lymphocytes, dendritic cells, and scar associated matrix molecules laminin, fibronectin, tenascin-C, and type III collagen. RESULTS: Populations of cells using markers for macrophages, leucocytes and antigen presenting cells were found to be associated with the epithelium and stroma of keratoconic tissue. Populations of these cells appeared decreased in hydrops-associated keratoconus except for a large increase in leucocytes in the stroma and endothelium associated with neovascularization. Extracellular matrix deposition was found to be uniquely demonstrated in localized areas of the stroma, corresponding to the site of hydrops involvement. CONCLUSIONS: Immunohistochemical analysis revealed a chronic, inflammatory process with recruitment of immunoinflammatory cells and deposition of scar tissue in keratoconus. The inflammatory markers were somewhat attenuated in hydrops-associated keratoconus corneas and thus inflammation was not considered to be a major factor in the development of acute corneal hydrops.

The expression of interleukin-1 alpha, TNF and VEGF in corneal cells of patients with bullous keratopathy.

Bullous keratopathy (BK) is a chronic corneal edema with or without subepithelial bullae as a result of a loss of the endothelial cells. 15 patients with BK after cataract surgery with intraocular lens implantation, due to Fuchs dystrophy (n = 3) or corneal endothelial trauma (n = 12) were included in the study. All patients were treated by amniotic membrane transplantation (AMT). Corneal epithelial cells in patients suffering from BK secreted 3.91 +/- 3.09 pg/mL of IL-1 alpha, 4446 +/- 16.8 pg/mL of TNF and 81.43 +/- 37.81 pg/mL of VEGF-I. Levels of all 3 investigated cytokines were significantly higher as compared to controls (p < 0.005). Amniotic membranes that were used to treat investigated patients contained 638.98 +/- 613.98 pg/mL of IL-1ra, 0.026 +/- 0.009 pg/mL of sTNF and 81.39 +/- 21.01 pg/mL of VEGF-R. Beneficial clinical effect of the AMT in treating BK could be explained by its natural production of pro-inflammatory cytokine antagonists such as IL-ra, sTNF antagonist and VEGF-R.

Severe corneal changes following intravitreal injection of bevacizumab.

PURPOSE: To report a series of severe corneal changes following intravitreal injection of bevacizumab (Avastin) for age-related macular degeneration. DESIGN: Retrospective noncomparative case series. METHODS: The authors retrospectively reviewed the corneal changes that developed after the procedure in 1200 (460 patients) intravitreal injections of bevacizumab. RESULTS: Five significant corneal changes (1.1%) occurred in these patients within the 1st postinjection week. The severe corneal changes included corneal infiltrative keratitis (n = 2) and corneal stromal edema and descemet folds (n = 3). The findings depended on clinical examination and biomicroscopic and confocal evaluation. In terms of causality assessment, no rechallenge was possible. The appropriate treatment was applied and recovery was achieved in all patients during the follow-up period. CONCLUSIONS: Intravitreal injection of bevacizumab may cause corneal changes. The safety and effects of bevacizumab on the cornea should be evaluated in detail.

[Ocular onchocerciasis: a key role for Wolbachia]. / Okuläre Onchozerkose: Wolbachien haben eine Schlüsselrolle.

Onchocerciasis is caused by the parasitic worm Onchocerca volvulus, which releases millions of offspring (microfilariae). Microfilariae migrate through the skin and can enter the anterior or posterior regions of the eye. While alive, the microfilariae appear to cause little or no inflammation, being in the anterior chamber. However, when they die, either by natural attrition or after chemotherapy, the host response to degenerating worms can result in ocular inflammation (keratitis, uveitis, chorioretinitis, neuritis of the optic nerve) that causes progressive loss of vision and ultimately leads to blindness. With the use of a mouse model of corneal inflammation to study the pathogenesis of ocular onchocerciasis by injecting worm extracts directly into the corneal stroma, it was found that worms treated with the antibiotic doxycycline, which destroys Wolbachia, induced lower corneal stromal thickness and stromal haze (indicators of corneal oedema and opacity) and neutrophil infiltration compared with both untreated worms and worms that do not harbour Wolbachia. These data indicate that endosymbiotic Wolbachia bacteria in filarial parasites have a key role in the pathogenesis of river blindness. Worms recovered from patients treated for 6 weeks with doxycycline contained fewer Wolbachia bacteria and had abnormal embryogenesis, indicating a role for Wolbachia in the survival or fecundity of the worms. Antibiotic treatment may also reduce the severity of the inflammatory response in the cornea.

Analysis of corneal inflammation induced by cauterisation in CCR2 and MCP-1 knockout mice.

AIM: To elucidate the role of CCR2/MCP-1 in corneal inflammation. METHODS: A cauterisation induced corneal inflammation model was used. The corneas were cauterised with silver nitrate in CCR2 knockout (KO) mice, MCP-1 KO mice, and control mice. Clinical signs such as corneal oedema and opacity were examined 96 hours after cauterisation and the phenotypes of the cells infiltrating the cornea were analysed by flow cytometry. Corneal inflammation in neutrophil depleted mice was also analysed. RESULTS: After cauterisation both CCR2 KO and MCP-1 KO mice showed the same levels of corneal oedema and opacity as control mice. Flow cytometry revealed that in control mice most of the infiltrating cells were neutrophils and macrophages, whereas in both CCR2 KO mice and MCP-1 KO mice, the number of macrophages infiltrating the cornea were markedly reduced. However, prominent infiltrates of neutrophils were still observed in the cornea in CCR2 KO mice and MCP-1 KO mice. The depletion of neutrophils significantly reduced the oedema and opacity induced in the cornea by cauterisation. CONCLUSION: The CCR2 and MCP-1 molecules are not essential for cauterisation induced corneal inflammation. Neutrophils, rather than migrated macrophages, are the final effector cells involved in inducing inflammation in this model.