Emerging Viral Infections Causing Anterior Uveitis

Purpose: To review the systemic and ocular manifestations of specific emergent viral infectious diseases relevant to the ophthalmologist with particular emphasis on anterior uveitis

Methods: Review of literature.

Results: Arboviral diseases are among the most important emergent and resurgent human infections, occurring mostly in tropical and subtropical zones, but appearing in virtually all regions of the world as a result of climate change, travel, and globalization. Arboviral infections are transmitted to humans by the bite of hematophagous arthropods, mainly mosquitoes. Systemic disease may range from asymptomatic to life-threatening. A wide variety of ocular manifestations, including uveitis, has been reported in association with these emerging viral diseases. Numerous viruses other than arboviruses also have been recently recognized as a potential cause of uveitis.

Conclusions: Proper clinical diagnosis of any emerging infectious disease is based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. The diagnosis is usually confirmed by detection of virus-specific DNA or antivirus antibodies in serum.     

Carbonic anhydrase gene expression in CA II-deficient (Car2−/−) and CA IX-deficient (Car9−/−) mice

Using real-time PCR and immunohistochemistry, we have examined the expression of carbonic anhydrase isozymes (CA) I, II, III, IV, IX, XII, XIII and XIV in the brain, kidney, stomach and colon of the wild-type, CA II-deficient ( Car2^−/− ), and CA IX deficient ( Car9^−/− ) mice. The expression of Car4, Car12, Car13 and Car14 mRNAs did not show any significant deviations between the three groups of mice, whereas both groups of CA deficient mice showed decreased expression levels of Car1 in the colon and Car3 in the kidney. The Car2 mRNA level was greatly reduced but not completely abolished in all four tissues from the Car2^−/− mice in which no CA II protein was expressed. Sequencing the Car2 cDNA isolated from C57BL6 Car2^−/− mice revealed two nucleotide differences from the wild-type C57BL6 mice. One is a silent polymorphism found in Car2 mRNA from wild-type DBA mice, which is the strain that provided the original mutagenized chromosome. The second change is a mutation that causes prematurely terminated translation at codon 155 (Gln155X). Car9 mRNA and CA IX protein expression levels were up-regulated about 2.5- and 3.6-fold, respectively, in the stomach of the Car2^−/− mice. These results suggest that the loss of function of cytosolic CA II in the stomach of Car2^−/− mice leads to up-regulation of an extracellular CA, namely CA IX, which is expressed on the cell surface of the gastric epithelium.     

CX3CL1 (fractalkine) and CX3CR1 expression in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis: kinetics and cellular origin

Background  

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). It is associated with local activation of microglia and astroglia, infiltration of activated macrophages and T cells, active degradation of myelin and damage to axons and neurons. The proposed role for CX₃CL1 (fractalkine) in the control of microglia activation and leukocyte infiltration places this chemokine and its receptor CX₃CR1 in a potentially strategic position to control key aspects in the pathological events that are associated with development of brain lesions in MS. In this study, we examine this hypothesis by analyzing the distribution, kinetics, regulation and cellular origin of CX₃CL1 and CX₃CR1 mRNA expression in the CNS of rats with an experimentally induced MS-like disease, myelin oligodendrocyte glycoprotein (MOG)-induced autoimmune encephalomyelitis (EAE).     

The effects in vivo of purified preparations of murine macrophage colony stimulating factor-1, recombinant murine granulocyte-macrophage colony stimulating factor and natural and recombinant murine interleukin 3 without and with pretreatment of mice with purified iron-saturated human lactoferrin

The influence of purified natural colony stimulating factor-1 (CSF-1), purified recombinant granulocyte-macrophage (GM)-CSF, purified recombinant interleukin 3 (IL3) and natural IL3 were assessed in mice that were untreated or pretreated with purified iron-saturated human lactoferrin (LF) in order to first suppress myelopoiesis in the mice. S1/S1d mice responded to recombinant GM-CSF and recombinant IL3 in a manner similar to the response of their +/+ littermates. These 4 factors increased the cycling status of hematopoietic progenitors in vivo. The effects were more noticeable if myelopoiesis was first decreased by LF. The effects do not appear to be due to endotoxin contamination. It cannot be discerned from these studies whether the effects are direct ones on the progenitor cells or indirect ones mediated through growth-factor releasing accessory cells. It is possible that effects can be both direct and indirect.     

Temporal expression and cellular origin of CC chemokine receptors CCR1, CCR2 and CCR5 in the central nervous system: insight into mechanisms of MOG-induced EAE

Background  

The CC chemokine receptors CCR1, CCR2 and CCR5 are critical for the recruitment of mononuclear phagocytes to the central nervous system (CNS) in multiple sclerosis (MS) and other neuroinflammatory diseases. Mononuclear phagocytes are effector cells capable of phagocytosing myelin and damaging axons. In this study, we characterize the regional, temporal and cellular expression of CCR1, CCR2 and CCR5 mRNA in the spinal cord of rats with myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE). While resembling human MS, this animal model allows unique access to CNS-tissue from various time-points of relapsing neuroinflammation and from various lesional stages: early active, late active, and inactive completely demyelinated lesions.     

The effects of interleukins and other soluble factors on T-lymphocyte colony formation.

When plated in semi-solid media, PHA-stimulated human peripheral blood mononuclear cells (PBMC) form discrete T-cell colonies. By contrast, Sephadex G-10 non-adherent (NA) cells (greater than 96% T lymphocytes) show virtually no clonal growth unless cocultured with soluble factors derived from either normal adherent cells or tumour cell lines. Purified IL-1 was able to initiate colony growth of mitogen-stimulated NA cells; cultures containing 20 U of human IL-1 yielded colony counts that were only slightly less than those with PBMC. In addition, recombinant IL-2, free of measurable IL-1, was able to provide the initiating signal required for clonal expansion. Both recombinant and lymphocyte-derived IL-2 were able to enhance the clonal growth of PBMC. Colony growth could be initiated by supernatants derived from short-term cultures of either monocytic (U937, HL60) or B-cell (Raji, Daudi) tumour cell lines. The abilities of these tumour cell lines to promote clonal responses did not correlate with their contents of either IL-1 or IL-2. By contrast, supernatants derived from either K562 (an erythroleukaemic line) or MOLT 4 (a T-cell lymphoma) cells did not provide the initiating signal.     

Overexpression of collagen XVIII is associated with poor outcome and elevated levels of circulating serum endostatin in non-small cell lung cancer.

PURPOSE: The aim of this study was to determine whether collagen XVIII expression is correlated with circulating serum endostatin and whether this has any prognostic value in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Serum endostatin levels were measured quantitatively by a competitive enzyme immunoassay, and collagen XVIII expression in tumor tissue was investigated with an immunohistochemical method in a series of 94 patients who underwent surgery for NSCLC. RESULTS: Sixty cases (63.8%) had positive immunohistochemical staining with anticollagen XVIII polyclonal antibodies, including strongly positive staining in 11 (11.7%) cases. The mean (+/- SD) serum endostatin level was 41.6 +/- 34.4 ng/ml in the patient group and 16.3 +/- 10.3 ng/ml in the control group (P < 0.0001). The 11 cases who were strongly collagen XVIII-positive had significantly higher serum endostatin levels than the cases who were negative or weakly positive (P = 0.0297). The 5-year survival rates of negative, weakly positive, and strongly positive patients were 77.8%, 56.9%, and 43.8%, respectively. The cases with strongly positive collagen XVIII expression had a significantly poorer outcome than cases with negative expression (P = 0.0027). A multivariate analysis with Cox proportional hazards model for disease-specific survival revealed that expression of collagen XVIII (strongly positive versus negative; weakly positive versus negative), tumor classification, and regional lymph node classification were independent prognostic factors. CONCLUSIONS: Our results suggest that expression of collagen XVIII in tumor tissue is strongly associated with a poorer outcome in NSCLC and correlates with elevated levels of circulating serum endostatin.     

稳定型圆锥角膜患者植入新型Phakic角膜接触镜的视觉效果分析

目的：评估可植入式Phakic角膜接触镜治疗稳定型圆锥角膜患者的疗效、安全性、稳定性和可预测性。

方法：共14例患者采用植入式Phakic角膜接触镜(IPCL)矫正屈光不正,测量了未矫正视力、最佳矫正视力、离焦曲线、对比敏感度、屈光度及可能的副作用。评估结果超过6mo。

结果：平均等效球镜度(SE)和散光在术后6mo末次检查时由术前-6.94±2.79 DS和-4.24±1.42 DC分别变为术后-0.23±0.43 DS和-1.05±0.49 DC。术前平均Snellen视力为0.18±0.10。6mo内未矫正视力和最佳矫正视力平均值分别为0.13±0.10和0.05±0.15。平均安全指数为1.11。所有眼视力均无降低,其中22眼视力提高超过1行。20眼(71.4%)屈光度在0.50 D以内,27眼(96.42%)在±1.00 D以内。术后1wk至6mo,屈光度变化为-0.23±0.43(范围： -1.00至+0.75)。6mo内角膜内皮细胞(ECL)丢失率小于5%。术后6mo眼压(IOP)为11.32±2.28 mmHg。

结论：Toric植入式Phakic角膜接触镜在矫正与稳定圆锥角膜相关的近视和近视散光方面具有有效性、安全性和可预测性。