Synergistic Induction of Eotaxin and VCAM-1 Expression in Human Corneal Fibroblasts by Staphylococcal Peptidoglycan and Either IL-4 or IL-13

Background: Common features of allergic or atopic ocular and skin diseases are the participation of Th2 lymphocytes and eosinophils and colonization by Staphylococcus aureus. To examine the role of interaction between Th2 cells and bacterial infection in tissue eosinophilia, we determined the effects of Th2 cytokines and peptidoglycan derived from the cell wall of S. aureus on corneal fibroblasts. Methods: Chemokine concentrations and the cell surface expression of adhesion molecules were determined by ELISAs, and chemokine and adhesion molecule mRNAs were quantitated by real-time PCR analysis. Signaling by the transcription factor NF-κB was evaluated by immunoblot and immunofluorescence analyses as well as by assay of dNa binding activity. Results: Among Th2 cytokines tested, only interleukin (IL)-4 and IL-13 induced a low level of eotaxin release by corneal fibroblasts, as did peptidoglycan. However, the combination of peptidoglycan and either IL-4 or IL-13 induced a marked synergistic increase both in eotaxin release (without affecting that of IL-8) and in the abundance of eotaxin mRNA. The combination of peptidoglycan and IL-4 or IL-13 also synergistically increased the surface expression of VCAM-1, but not that of ICAM-1. Peptidoglycan activated NF-κB in corneal fibroblasts, and inhibitors of NF-κB attenuated eotaxin release induced by peptidoglycan alone or in combination with IL-4 or IL-13. Conclusions: Interaction of innate and adaptive immunity, as manifested by synergistic stimulation of eotaxin and VCAM-1 expression in corneal fibroblasts by peptidoglycan and Th2 cytokines, may play an important role in tissue eosinophilia associated with ocular allergy

Corneal Fibroblasts as Sentinel Cells and Local Immune Modulators in Infectious Keratitis

The cornea serves as a barrier to protect the eye against external insults including microbial pathogens and antigens. Bacterial infection of the cornea often results in corneal melting and scarring that can lead to severe visual impairment. Not only live bacteria but also their components such as lipopolysaccharide (LPS) of Gram-negative bacteria contribute to the development of inflammation and subsequent corneal damage in infectious keratitis. We describe the important role played by corneal stromal fibroblasts (activated keratocytes) as sentinel cells, immune modulators, and effector cells in infectious keratitis. Corneal fibroblasts sense bacterial infection through Toll-like receptor (TLR)–mediated detection of a complex of LPS with soluble cluster of differentiation 14 (CD14) and LPS binding protein present in tear fluid. The cells then initiate innate immune responses including the expression of chemokines and adhesion molecules that promote the recruitment of inflammatory cells necessary for elimination of the infecting bacteria. Infiltrated neutrophils are activated by corneal stromal collagen and release mediators that stimulate the production of pro–matrix metalloproteinases by corneal fibroblasts. Elastase produced by Pseudomonas aeruginosa (P. aeruginosa) activates these released metalloproteinases, resulting in the degradation of stromal collagen. The modulation of corneal fibroblast activation and of the interaction of these cells with inflammatory cells and bacteria is thus important to minimize corneal scarring during treatment of infectious keratitis. Pharmacological agents that are able to restrain such activities of corneal fibroblasts without allowing bacterial growth represent a potential novel treatment option for prevention of excessive scarring and tissue destruction in the cornea

Unilateral serous retinal detachment with choroidal thickening as a first presenting sign of acute myeloid leukemia

Purpose: Serous retinal detachment is rare in leukemia, but bilateral or unilateral cases have been reported as the presenting sign of acute leukemia or the first sign of relapsing leukemia. We here report a case of unilateral serous retinal detachment with choroidal thickening before the detection of atypical lymphocytes or myeloblasts as the initial manifestation of subsequently diagnosed acute myeloid leukemia. Observations: A 43-year-old woman presented with serous retinal detachment in her left eye. Choroidal thickening was also revealed by B-scan ultrasonography and optical coherence tomography. Atypical lymphocytes or myeloblasts were not apparent on hematologic analysis at initial presentation, but an increased leukocyte count and the presence of 40% blasts in a peripheral smear were detected 1 month later. A bone marrow biopsy led to a diagnosis of acute promyelocytic leukemia. The retinal detachment and choroidal thickening showed amelioration 4 days after the onset of chemotherapy and had resolved 2 months later. Conclusions and importance: The present findings suggest that, although retinal detachment is not a common manifestation in patients with leukemia, unilateral serous retinal detachment with choroidal thickening may be a presenting sign of acute myeloid leukemia. Keywords: Serous retinal detachment, Leukemia, Choroidal thickening, Chemotherapy, B-scan ultrasonograph

A Case of Functional (Psychogenic) Monocular Hemianopia Analyzed by Measurement of Hemifield Visual Evoked Potentials

Purpose: Functional monocular hemianopia is an extremely rare condition, for which measurement of hemifield visual evoked potentials (VEPs) has not been previously described. Methods: A 14-year-old boy with functional monocular hemianopia was followed up with Goldmann perimetry and measurement of hemifield and full-field VEPs. Results: The patient had a history of monocular temporal hemianopia of the right eye following headache, nausea and ague. There was no relative afferent pupillary defect, and a color perception test was normal. Goldmann perimetry revealed a vertical monocular temporal hemianopia of the right eye; the hemianopia on the right was also detected with a binocular visual field test. Computed tomography, magnetic resonance imaging (MRI) and MR angiography of the brain including the optic chiasm as well as orbital MRI revealed no abnormalities. On the basis of these results, we diagnosed the patient's condition as functional monocular hemianopia. Pattern VEPs according to the International Society for Clinical Electrophysiology of Vision (ISCEV) standard were within the normal range. The hemifield pattern VEPs for the right eye showed a symmetrical latency and amplitude for nasal and temporal hemifield stimulation. One month later, the visual field defect of the patient spontaneously disappeared. Conclusions: The latency and amplitude of hemifield VEPs for a patient with functional monocular hemianopia were normal. Measurement of hemifield VEPs may thus provide an objective tool for distinguishing functional hemianopia from hemifield loss caused by an organic lesion