An Ocular Protein Triad Can Classify Four Complex Retinal Diseases.

Retinal diseases generally are vision-threatening conditions that warrant appropriate clinical decision-making which currently solely dependents upon extensive clinical screening by specialized ophthalmologists. In the era where molecular assessment has improved dramatically, we aimed at the identification of biomarkers in 175 ocular fluids to classify four archetypical ocular conditions affecting the retina (age-related macular degeneration, idiopathic non-infectious uveitis, primary vitreoretinal lymphoma, and rhegmatogenous retinal detachment) with one single test. Unsupervised clustering of ocular proteins revealed a classification strikingly similar to the clinical phenotypes of each disease group studied. We developed and independently validated a parsimonious model based merely on three proteins; interleukin (IL)-10, IL-21, and angiotensin converting enzyme (ACE) that could correctly classify patients with an overall accuracy, sensitivity and specificity of respectively, 86.7%, 79.4% and 92.5%. Here, we provide proof-of-concept for molecular profiling as a diagnostic aid for ophthalmologists in the care for patients with retinal conditions.

Molecular and Serological Intraocular Fluid Analysis of Coxiella burnetii-seropositive Patients with Concurrent Idiopathic Uveitis.

PURPOSE: Previous studies have suggested a link between Q fever and uveitis. We determined whether Coxiella burnetii causes intraocular infection in C. burnetii-seropositive patients with idiopathic uveitis. METHODS: From a retrospective observational case series, paired aqueous humor and serum samples from 10 C. burnetii-seropositive patients with idiopathic uveitis were examined for intraocular antibody production by using the Goldmann-Witmer coefficient and by polymerase chain reaction (PCR). RESULTS: Although intraocular IgG against C. burnetii was detected, no intraocular antibody production was observed (low Goldmann Wittmer coefficients). All PCR results were negative. CONCLUSIONS: Uveitis due to an intraocular infection with C. burnetii is unlikely.

Viral causes of unexplained anterior uveitis in Thailand.

AIMS: To assess the possible role of virus infection in patients with unexplained anterior uveitis (AU). METHODS: Intraocular fluid and plasma samples of 30 HIV-negative AU patients who were unresponsive or poorly responsive to topical steroid therapy were analyzed for nucleic acid of cytomegalovirus (CMV), herpes simplex virus (HSV), and varicella zoster virus (VZV) by real-time polymerase chain reaction (PCR) and for intraocular antibodies against these viruses by Goldmann-Witmer coefficient (GWC) analysis. Of these 30 cases, 21 were tested for rubella virus by GWC analysis, 16 of which also had PCR assessment of aqueous for rubella virus. RESULTS: Viral uveitis determined by either real-time PCR and/or GWC was documented in 20 out of 30 patients (67%). Of 30 paired samples tested by both methods for HSV, CMV, and VZV, 15 showed positive results (CMV (10), HSV (4), and VZV (1)). Real-time PCR was positive in 8/15 (53%), whereas GWC was positive in 10/15 (67%). Out of 10 CMV-positive patients, four had endotheliitis, two had Posner-Schlossman syndrome, and one Fuchs heterochromic uveitis syndrome (FHUS). Five out of 21 (24%) samples tested by GWC for Rubella virus were positive, three of which exhibited clinical features of FHUS. CONCLUSIONS: Our results indicate that CMV is a major cause of AU in Thailand and show that FHUS can be caused by both CMV and Rubella virus.

[Relationship between rubella virus and Fuchs heterochromic uveitis; 2 patients]. / Samenhang tussen rubellavirus en fuchs-heterochromie-uveïtis; 2 patiënten.

Two otherwise healthy men, aged 26 and 29 years, were diagnosed with Fuchs heterochromic uveitis (FHU) on the basis of the presence of iris heterochromia or iris atrophy, stellate corneal precipitates, and/or cataract. Microbiological investigation of aqueous humour demonstrated intraocular antibody production against rubella virus, but not against Toxoplasma gondii, herpes simplex virus or varicella zoster virus. Microbial nucleic acid detection was negative for all pathogens. Some time later, both patients underwent cataract surgery, which improved their vision considerably. FHU is a chronic, generally unilateral iridocyclitis, accompanied by the above-mentioned ophthalmologic manifestations in the absence of systemic disease. Little is known about the pathogenesis ofFHU, but recent publications have provided evidence for the possible involvement of the rubella virus.

Luxury at a cost? Recombinant mouse hepatitis viruses expressing the accessory hemagglutinin esterase protein display reduced fitness in vitro.

Group 2 coronaviruses encode an accessory envelope glycoprotein species, the hemagglutinin esterase (HE), which possesses sialate-O-acetylesterase activity and which, presumably, promotes virus spread and entry in vivo by facilitating reversible virion attachment to O-acetylated sialic acids. While HE may provide a strong selective advantage during natural infection, many laboratory strains of mouse hepatitis virus (MHV) fail to produce the protein. Apparently, their HE genes were inactivated during cell culture adaptation. For this report, we have studied the molecular basis of this phenomenon. By using targeted RNA recombination, we generated isogenic recombinant MHVs which differ exclusively in their expression of HE and produce either the wild-type protein (HE+), an enzymatically inactive HE protein (HE0), or no HE at all. HE expression or the lack thereof did not lead to gross differences in in vitro growth properties. Yet the expression of HE was rapidly lost during serial cell culture passaging. Competition experiments with mixed infections revealed that this was not due to the enzymatic activity: MHVs expressing HE+ or HE0 propagated with equal efficiencies. During the propagation of recombinant MHV-HE+, two types of spontaneous mutants accumulated. One produced an anchorless HE, while the other had a Gly-to-Trp substitution at the predicted C-terminal residue of the HE signal peptide. Neither mutant incorporated HE into virion particles, suggesting that wild-type HE reduces the in vitro propagation efficiency, either at the assembly stage or at a postassembly level. Our findings demonstrate that the expression of "luxury" proteins may come at a fitness penalty. Apparently, under natural conditions the costs of maintaining HE are outweighed by the benefits.