Takeshi Fujimoto

Choroidal Neovascularization Enhanced by Chlamydia pneumoniae via Toll-like Receptor 2 in the Retinal Pigment Epithelium

PURPOSE Choroidal neovascularization (CNV) is directly related to visual loss in persons with age-related macular degeneration (AMD) and other macular disorders. Chlamydia pneumoniae, a prokaryotic pathogen that causes chronic inflammation, is recognized as a risk factor for cardiovascular diseases. In this study, the authors investigated the association between C. pneumoniae infection and AMD using a laser-induced CNV model in mice. METHODS C57BL/6 mice, myeloid differentiation factor (MyD) 88 knockout (KO) mice, Toll-like receptor (TLR) 2 KO mice, and TLR4 KO mice were used. Experimental CNV was induced by rupturing the Bruchs membrane by laser photocoagulation (PC). Seven days after PC, the eyes were enucleated and the areas of CNV were measured in choroidal flat mounts. Cytokine gene expression by quantitative real-time PCR in the primary cultured retinal pigment epithelium (RPE) cells was also examined. RESULTS Vitreous injection of the C. pneumoniae antigen increased the size of CNV. Although lipopolysaccharide stimulation can induce multiple cytokines, cultured mouse RPE cells from C57BL/6 mice expressed IL-6 and VEGF, but not TNF-alpha mRNA, in response to C. pneumoniae antigen. RPE cells from either MyD88 KO mice or TLR2 KO mice did not respond to the C. pneumoniae antigen. TLR2 KO mice did not augment the size increase of experimental CNV by C. pneumoniae antigen in vivo. CONCLUSIONS C. pneumoniae can trigger inflammatory responses in the eye and promote experimental CNV in a TLR2-dependent manner. These data provide experimental evidence to imply persistent C. pneumoniae infection is a risk factor for AMD.

Acquired resistance to infliximab against uveitis due to Behçet's disease after one year of administration

most likely cause of the late-onset haptic disinsertion from the IOL. Even if fatigue of the haptic–optic junction led to the haptic disinsertion, the supportive capsular bag surrounding the IOL should have prevented the IOL from dislocating into the anterior chamber, as in one of the two cases reported by Solano et al. Several causes of the anterior dislocation of the IOL in our patient are possible. First, progressive fatigue in the haptic–optic junction or haptic disinsertion from the optic may have existed before the episode we observed. Second, the anterior capsulotomy during ECCE surgery may have been performed by the can-opener method, which can result in a larger and less intact anterior capsular rim than with the currently used continuous circular capsulorhexis method. Third, this episode apparently occurred when the patient bent forward to wash his face in the dark. An acute rise in intraocular pressure (IOP) caused by physiological changes, including increases in aqueous infl ow, in resistance to aqueous outfl ow, and in episcleral venous pressure after the body position is altered, can induce anterior movement of the lens–iris diaphragm. Along with haptic–optic junction fatigue or existing haptic disinsertion from the optic, an immediate rise in IOP when the patient bent forward may also have caused a posterior pressure gradient leading to the anterior dislocation of the IOL in our patient with incomplete optic fi xation in the capsular bag and a dilated pupil in the dark. In theory, haptic disinsertion as a complication in the case of a one-piece IOL is impossible. However, intraoperative or postoperative traumatic fractures of one-piece IOLs have been reported, but without any ill effects of the fracture in the periphery of the one-piece silicon IOL at the 3-month follow-up. On the basis of our case of late-onset spontaneous IOL dislocation, we do not think it advisable to keep a fractured one-piece IOL in the bag in certain circumstances, especially when the anterior capsular rim is not intact or when it is larger than the size of the optic. Late-onset nontraumatic optic dislocation with haptic disinsertion from a three-piece IOL is a rare long-term complication after cataract surgery. Progressive fatigue of the haptic–optic junction may cause haptic disinsertion, and a head-down position with pupil dilatation in the dark may result in subsequent spontaneous IOL dislocation. Delicate surgical techniques and careful selection of IOL products are important to prevent such a complication.

Investigation of the role of CD1d-restricted invariant NKT cells in experimental choroidal neovascularization.

Choroidal neovascularization (CNV) is directly related to visual loss in age-related macular degeneration and other macular disorders. We have investigated the role of CD1d-restricted invariant natural killer T (NKT) cells in laser-induced experimental CNV. Quantitative real-time PCR detected increased expression of NKT cell-related genes (Valpha14 and CXCL16) in whole eyes undergoing CNV, indicating local accumulation of NKT cells. We found a significant reduction of CNV and lower concentrations of vascular endothelial growth factor (VEGF) in ocular fluid in two different NKT cell-deficient mice, CD1d knockout (KO) and Jalpha18 KO mice. We also established in vitro co-cultures of retinal pigment epithelial cells and splenic NKT cells, and confirmed NKT cells could produce VEGF in the dish. Moreover, inoculating alpha-galactosylceramide, the ligand for NKT cells, into the vitreous cavity of C57BL/6 mice promoted CNV. We concluded that NKT cells play an important role in CNV as an inducer of VEGF.