Sweeping technique for the removal of emulsified silicone oil droplets from the anterior surface of the iris using an ophthalmic absorption sponge.

PURPOSE: Silicone oil (SO) tamponade is frequently used in complex vitreoretinal surgeries, and SO migration into the anterior chamber can lead to complications such as glaucoma and corneal decompensation. A new technique is described for the efficient removal of emulsified SO droplets, which can adhere strongly to the anterior surface of the iris. METHODS: The tip of an ophthalmic absorption sponge was cut to an approximately 1x1 mm size. Using forceps, the sponge was inserted through a 25-gauge trocar, then through a corneal paracentesis, to gently scrape the surface of the iris to dislodge the adherent SO droplets, which were subsequently aspirated. RESULTS: This technique efficiently and effectively dislodged and mobilized most emulsified SO droplets, thereby allowing removal via aspiration using a vitrector. Two months after surgery, the retina remained attached, the intraocular pressure decreased from 18 mmHg to 15 mmHg, and there were no visible SO droplets in the anterior chamber. CONCLUSION: The sweeping technique is a safe and efficient method to dislodge, mobilize and aspirate emulsified SO droplets that are adherent to the anterior surface of the iris, thereby decreasing the risk of future SO-related complications.

Anti-hepatitis C Virus Activity of Juglorubin Derivatives.

Juglorubin is a natural dye isolated from the culture of Streptomyces sp. 3094, 815, and GW4184. It has been previously synthesized via the biomimetic dimerization of juglomycin C, a plausible genetic precursor. In this study, the derivatives of juglorubin, 1-O-acetyljuglorubin dimethyl ester and juglorubin dimethyl ester, were found to exhibit antiviral activity against hepatitis C virus (HCV) without exerting any remarkable cytotoxicity against host Huh-7 cells. They also inhibited liver X receptor α activation and lipid droplet accumulation in Huh-7 cells. These findings suggest that 1-O-acetyljuglorubin dimethyl ester and juglorubin dimethyl ester targeted the host factors required for HCV production.

Surgical treatment of traction retinal detachment associated with compound heterozygous congenital protein C deficiency.

Purpose: Congenital protein C deficiency leads to a prothrombotic state that may result in potentially sight- and life-threatening thromboembolic attacks. In this report, we report two cases of infants with compound heterozygous protein C deficiency who underwent lensectomies and vitrectomies for the treatment of traction retinal detachments (TRDs). Observations: One two-month-old and one three-month-old female neonates with leukocoria and purpura fulminans received a diagnosis of protein C deficiency and were referred to ophthalmology. In both cases, the right eye had a total retinal detachment that was considered inoperable, while the left eye had a partial TRD for which surgery was performed. Of the two operated eyes, one resulted in a total retinal detachment, while the other eye has remained stable with no retinal detachment progression three months after surgery. Conclusions: Compound heterozygous congenital protein C deficiency may lead to the rapid development of severe TRDs with poor visual and anatomical prognoses. Early diagnosis and surgery for the treatment of partial TRDs with low disease activity may help prevent progression towards total retinal detachments in these infants.

Long-Term Visual Prognosis of Patients Following Lens-Sparing Vitrectomy for Stage 4A Retinopathy of Prematurity.

This study evaluated the long-term visual outcomes of patients in whom at least one eye underwent successful lens-sparing vitrectomy (LSV) for stage 4A retinopathy of prematurity (ROP). A retrospective chart review was conducted using the data of 61 eyes of 42 patients with a minimum 4-year follow-up after successful LSV, with or without anti-vascular endothelial growth factor (VEGF) therapy, and whose best-corrected visual acuity (BCVA) was measurable using Landolt rings at the final visit. The mean age at the final follow-up was 10.1 ± 3.3 years. Before LSV, all eyes underwent laser ablation therapy. Twenty eyes (32.8%) with high vascular activity received anti-VEGF therapy before LSV. The mean decimal BCVA at the final follow-up was 0.23 ± 0.26 (range: hand motion to 1.2). Twenty-three eyes (54.1%) had a decimal BCVA of ≥0.4. Among 49 phakic eyes at the final examination, the mean refractive error was -10.1 ± 5.0 D, with 37 eyes (75.5%) having high myopia (>-6.0 D). No significant differences were observed in terms of decimal BCVA and refractive errors between eyes with and without anti-VEGF therapy. Approximately half of the patients had a decimal BCVA of ≥0.4, despite myopic refraction after successful LSV for stage 4A ROP. LSV for stage 4A ROP seemed to be associated with good visual function, despite myopic refraction.

Flowability of Gel-Matrix and Magnetorheological Response for Carrageenan Magnetic Hydrogels.

The relationship between rheological features in the absence of a magnetic field and magnetic response was investigated for κ-carrageenan magnetic hydrogels containing carbonyl iron particles. The concentration of carrageenan was varied from 1.0 to 5.0 wt%, while the concentration of carbonyl iron was kept at 70 wt%. The magnetic response revealed that the change in storage modulus ΔG' decreased inversely proportional to the carrageenan concentration. A characteristic strain γ1 where G' equals to G″ was seen in a strain range of 10-3. It was found that ΔG' was inversely proportional to the characteristic stress at γ1. Another characteristic strain γ2 where the loss tangent significantly increased was also analyzed. Similar to the behavior of γ1, ΔG' was inversely proportional to γ2. The characteristic stresses at γ1 and γ2 were distributed at 80-720 Pa and 40-310 Pa, respectively. It was revealed that a giant magnetorheology higher than 1 MPa can be observed when the characteristic stresses at γ1 and γ2 are below approximately 240 Pa and 110 Pa, respectively.

An essential role for RPE-derived soluble VEGF in the maintenance of the choriocapillaris.

Clinical and experimental observations indicate a role for VEGF secreted by the retinal pigment epithelium (RPE) in the maintenance of the choriocapillaris (CC). VEGF in mice is produced as three isoforms, VEGF120, VEGF164, and VEGF188, that differ in their ability to bind heparan sulfate proteoglycan. RPE normally produces the more soluble isoforms, VEGF120 and VEGF164, but virtually no VEGF188, reflecting the fact that molecules secreted by the RPE must diffuse across Bruch's membrane (BrM) to reach the choriocapillaris. To determine the role of RPE-derived soluble VEGF on the choriocapillaris survival, we used mice that produce only VEGF188. VEGF188/188 mice exhibited normal choriocapillaris development. However, beginning at 7 months of age, we observed a progressive degeneration characterized by choriocapillaris atrophy, RPE and BrM abnormalities, culminating in areas of RPE loss and dramatic choroidal remodeling. Increased photoreceptor apoptosis in aged VEGF188/188 mice led to a decline in visual acuity as detected by electroretinogram (ERG). These changes are reminiscent of geographic atrophy (GA) and point to a role for RPE-derived VEGF in the maintenance of the choriocapillaris.

Role of cell and matrix-bound VEGF isoforms in lens development.

PURPOSE: To determine the role of vascular endothelial growth factor (VEGF) in embryonic eye development and lens differentiation. METHODS: Expression of components of the VEGF signaling pathway during lens development and in adults was characterized by beta-galactosidase staining of VEGF-LacZ mice, immunohistochemistry, and real-time (q) PCR. Embryonic eyes from wild-type mice and VEGF120/120 mice were analyzed by light microscopy and immunohistochemistry. VEGF function during lens development was analyzed using eye explants treated with VEGF-neutralizing antibody. Direct function of VEGF was demonstrated on the human lens epithelial cell line, HLE-B3. RESULTS: Embryonic lens epithelium and posterior lens fibers expressed VEGF and VEGFR2. qPCR revealed VEGF164 as the major isoform in embryonic lens. Transgenic mice expressing only VEGF120 (VEGF120/120 mice) showed major defects in eye development, including microphthalmia, failed lens differentiation, and hyperplastic hyaloid vessels. The lens displayed abnormal cell patterning and differentiation associated with altered c-Maf, Prox1, and p57 expression pattern in the anterior epithelium. The number of proliferating epithelial cells was drastically reduced in VEGF120/120 lenses. Altered MIP26 cellular localization and reduced E-cadherin expression in the lens epithelium were observed. VEGF-neutralization led to reduced fiber elongation of eye explants. Exogenous VEGF increased survival and proliferation of HLE-B3 cell in a dose-dependent manner. CONCLUSIONS: Abnormalities in ocular development in VEGF120/120 mice suggest a role for VEGF not only in the formation of ocular vascular beds but also in the differentiation of the lens itself.

Endogenous VEGF is required for visual function: evidence for a survival role on müller cells and photoreceptors.

BACKGROUND: Vascular endothelial growth factor (VEGF) is well known for its role in normal and pathologic neovascularization. However, a growing body of evidence indicates that VEGF also acts on non-vascular cells, both developmentally as well as in the adult. In light of the widespread use of systemic and intraocular anti-VEGF therapies for the treatment of angiogenesis associated with tumor growth and wet macular degeneration, systematic investigation of the role of VEGF in the adult retina is critical. METHODS AND FINDINGS: Using immunohistochemistry and Lac-Z reporter mouse lines, we report that VEGF is produced by various cells in the adult mouse retina and that VEGFR2, the primary signaling receptor, is also widely expressed, with strong expression by Müller cells and photoreceptors. Systemic neutralization of VEGF was accomplished in mice by adenoviral expression of sFlt1. After 14 days of VEGF neutralization, there was no effect on the inner and outer retina vasculature, but a significant increase in apoptosis of cells in the inner and outer nuclear layers. By four weeks, the increase in neural cell death was associated with reduced thickness of the inner and outer nuclear layers and a decline in retinal function as measured by electroretinograms. siRNA-based suppression of VEGF expression in a Müller cell line in vitro supports the existence of an autocrine role for VEGF in Müller cell survival. Similarly, the addition of exogenous VEGF to freshly isolated photoreceptor cells and outer-nuclear-layer explants demonstrated VEGF to be highly neuroprotective. CONCLUSIONS: These results indicate an important role for endogenous VEGF in the maintenance and function of adult retina neuronal cells and indicate that anti-VEGF therapies should be administered with caution.

Developmental expression patterns of the zebrafish small heat shock proteins.

Small heat shock proteins (sHSPs), or alpha-crystallins, are low-molecular weight proteins found in every kingdom and nearly every species examined to date. Many, if not all, sHSPs act as molecular chaperones. Several also have functions independent of their chaperone activity, and at least a few are expressed in specific spatiotemporal patterns during embryonic and/or juvenile stages, suggesting specific roles during development. To date, however, no one has systematically characterized the expression patterns of all of the sHSPs during development in any organism. We have characterized the normal heat shock-induced expression patterns of all 13 zebrafish sHSPs during development. Seven of the sHSPs are expressed in a tissue-specific manner during development, and five are upregulated by heat shock. The results of these studies provide a foundation for analysis of sHSP function during normal development and their roles in protecting cells from the effects environmental stressors.

Total synthesis of (-)-hennoxazole A.

An enantioselective, convergent total synthesis of the antiviral marine natural product (-)-hennoxazole A is completed in 14 steps (longest linear sequence) from commercially available 4-methyloxazole-2-carboxylic acid. Synthesis of the C(1)-C(15) pyran/bisoxazole fragment takes advantage of an aldol-like coupling between a dimethyl acetal and an N-acetylthiazolidinethione for the direct, stereoselective installation of the C(8)-methoxy-bearing stereocenter. A one-pot acetoacetate acylation/decarboxylation/cyclodehydration of another elaborate thiazolidinethione allows for rapid assembly of the pyran-based ring system. Synthesis of the C(15)-C(25) skipped triene side chain fragment makes use of a [2,3]-Wittig-Still rearrangement for efficient installation of the trisubstituted Z-double bond. Key late-stage coupling of the two fragments is effected by deprotonation of the methyl group on the bisoxazole system using lithium diethylamide, followed by alkylation with an allylic bromide side chain segment to form the C(15)-C(16) bond.