Herpes simplex keratitis and dendritic cells at the crossroads: lessons from the past and a view into the future.

Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
International Ophthalmology Clinics 02/2009; 49(1):53-62. DOI: 10.1097/IIO.0b013e3181924dd8
Source: PubMed
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recurrent herpes stromal keratitis (HSK) is one of the leading causes of blindness in the developed world. Cyokines characteristic of Th1 cells (in particular IFN-γ and IL-2) have been shown to dominate in HSK in addition to mechanisms by nonspecific, antigen-independent effector cells such as neutrophils, basophils, and monocytes. More recently, the migration and maturation of dendritic cells (DC) within the corneal stroma of patients with HSK have been recognized as contributors to recurrent disease, suggesting a role for delayed type hypersensitivity (DTH) in the immunopathogenesis of HSK. The role of DC and DTH in recurrent HSK has not been studied extensively and experimental models of recurrent HSK focusing on DTH as the pathogenesis and viral particles as the triggering antigen may contribute to better understanding of the disease.
    Seminars in ophthalmology 07/2011; 26(4-5):246-50. · 1.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: To investigate the characteristics of the inflammatory response detected in corneas with active non-epithelial herpes simplex virus (HSV) keratitis. Materials and methods: The study was designed as a cross-sectional study undertaken at a university setting. Twenty-one eyes of 21 patients with a mean age of 40.1 ± 13.0 years (range: 18-70 years) and whose corneal findings were compatible with active HSV keratitis were included. All patients were evaluated with in vivo confocal microscopy (Confoscan 3, Nidek). Fifty healthy, age-matched subjects served as controls. The features and extent of corneal inflammation, degree of involvement of subbasal nerve plexus and endothelial cell density were evaluated. Results: Seven eyes (33.3%) demonstrated stromal keratitis, six (28.6%) endotheliitis and eight (38.1%) presented with keratouveitis. Intraepithelial inflammatory cell infiltration, consisting of dendritic and small round cells, was observed in 11 eyes (52.4%). Stromal involvement was detected in 95.2% of eyes in the form of focal and diffuse cellular infiltrates; of these, anterior, posterior and pan stromal infiltration was observed in 85.7, 71.4 and 47.6% of cases, respectively. No particular keratic precipitate morphology was found to be diagnostic for HSV keratitis. The mean endothelial cell density of eyes with HSV keratitis (2437 ± 599 cells/mm(2)) was significantly lower (-18.8%) than that of controls (3003 ± 250 cells/mm(2)); (p < 0.001). The mean subbasal nerve density of patients with HSV keratitis (474.5 ± 227.8 μm/frame) was significantly lower than that of controls (1589.6 ± 499.0 μm/frame) (p < 0.001). Conclusions: Non-epithelial HSV keratitis related inflammatory response is characterized by cellular infiltration of all corneal layers, attenuation of the subbasal nerve plexus and endothelial cell loss.
    Current eye research 07/2012; · 1.51 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The peripheral cornea contains mature and immature resident dendritic cells (DCs) while the central cornea is exclusively equipped with immature DCs. There must be some factors that cause immature DCs. This study investigated whether corneal stroma cells (CSCs) inhibit DC maturation by secreting cytokines. The messenger ribonucleic acid (mRNA) and protein level of transforming growth factor beta 2 (TGF-β(2)) was analyzed using reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Immature DCs were induced to mature in the presence of lipopolysaccharide (LPS) and with concentrations of CSC culture supernatant (containing and not containing neutralizing TGF-β(2) antibodies). Then, the DC phenotypic and functional maturation were analyzed. CSCs exhibited positive expressions of TGF-β(2) mRNA and secreted high concentrations of TGF-β(2) protein. In the presence of LPS, DCs, which were treated with a CSC culture supernatant, displayed reduced expressions of cluster of differentiation 80 (CD80), CD86, and major histocompatibility complex II (MHC II) in a dose-dependent manner. Moreover, treated DCs showed lower T-cell stimulation capacity and a higher endocytosis function. However, these phenotypic and functional modifications were partially reversed after the application of neutralizing TGF-β(2) antibodies. This study demonstrates that CSCs can partially inhibit LPS-induced DC maturation through TGF-β(2) secretion in vitro.
    Molecular vision 01/2012; 18:2255-64. · 1.99 Impact Factor