Traumatic dislocation of the iris into the vitreous cavity with intact lens: a case report.

BACKGROUND: Traumatic aniridia occurs when the iris is extruded from the eye and is often accompanied by lens injuries. However, traumatic aniridia due to dislocation of the iris into the vitreous cavity without lens damage has never been reported. CASE PRESENTATION: A 30-year-old man presented with visual loss and pain for 6 h after a thin wire injured his right eyeball. Ophthalmologic examinations manifested a 2 mm full-thickness corneal laceration and total hyphema. An intact clear lens, healthy attached retina, and almost complete iris tissue in the vitreous cavity were found after resolution of hyphema the next day. Further examination revealed that the defect in the zonule below the corneal wound was the path for the iris to enter the vitreous cavity. The patient opted for nonsurgical treatment until pigment granules and opacity were observed in the vitreous cavity after 50 days. Vitrectomy was performed to remove the dislocated iris. CONCLUSIONS: The presentation of this unique case indicates that the torn iris was displaced to the vitreous cavity with an intact lens and missing local zonula instead of out the corneal laceration after a penetrating injury. The type of injury, mechanism, and force on the spot may contribute to the occurrence of this rare condition. Instead of artificial irises, tinted glasses were more appropriate treatment option for this patient. Peripheral retinal examination was essential in the management of this case. In such cases, the iris in the vitreous cavity should be resected to prevent complications.

Novel mutations in the BEST1 gene cause distinct retinopathies in two Chinese families.

AIM: To describe the clinical heterogeneity of patients with novel mutations in BEST1. METHODS: All the members in the two Chinese families underwent detailed clinical evaluations including best-corrected visual acuity, slit-lamp examination, applanation tonometry, and dilated fundus examination. Fundus autofluorescence, fundus fluorescein angiography, spectral-domain optical coherence tomography, electrooculography, and electroretinogram were also performed. Genomic DNA was extracted from venous blood for all the participants. The targeted next-generation sequencing of inherited retinal disease-associated genes was conducted to identify the causative mutation. RESULTS: A novel BEST1 missense mutation c.41T>C (p.Leu14Ser) was identified in Family 1. It was co-segregated with the phenotype of best vitelliform macular dystrophy (BVMD) and bioinformatics analysis confirmed it was harmful. Another novel BEST1 frameshift mutation c.345_346insGGCAAGGACG (p.Glu119Glyfs*116) and a novel USH2A missense mutation c.12560G>A, p.Arg4187His were identified in family 2 with retinitis pigmentosa (RP), which might interact and lead to the phenotype of RP. CONCLUSION: Two novel mutations in the BEST1 gene in two unrelated families with distinct phenotypes and BEST1 mutation accompanied with USH2A mutation would result in RP, which could be enormously helpful in understanding the pathogenesis of the inherited retinal disease caused by a BEST1 mutation.

Ag@TiO2 Nanoprisms with Highly Efficient Near-Infrared Photothermal Conversion for Melanoma Therapy.

Melanoma is a primary reason of death from skin cancer and associated with high lethality. Photothermal therapy (PTT) has been developed into a powerful cancer treatment technique in recent years. Here, we created a low-cost and high-performance PTT agent, Ag@TiO2 NPs, which possesses a high photothermal conversion efficiency of ≈65 % and strong near-infrared (NIR) absorption about 808 nm. Ag NPs were synthesized using a two-step method and coated with TiO2 to obtain Ag@TiO2 NPs by a facile sol-gel method. Because of the oxide, Ag@TiO2 NPs exhibit remarkable high photothermal conversion efficiencies and biocompatibility in vivo and in vitro. Cytotoxicity and therapeutic efficiency of photothermal cytotoxicity of Ag@TiO2 NPs were tested in B16-F10 cells and C57BL/6J mice. Under light irradiation, the elevated temperature causes cell death in Ag NPs-treated (100 µg mL-1 ) cells in vitro (both p<0.01). In the case of subcutaneous melanoma tumor model, Ag@TiO2 NPs (100 µg mL-1 ) were injected into the tumor and irradiated with a 808 nm laser of 2 W cm-2 for 1 minute. As a consequence, the tumor volume gradually decreased by NIR laser irradiation with only a single treatment. The results demonstrate that Ag@TiO2 NPs are biocompatible and an attractive photothermal agent for cutaneous melanoma by local delivery.

A novel mutation of FOXC1 in a Chinese family with Axenfeld-Rieger syndrome.

Axenfeld-Rieger syndrome (ARS) is a disorder affecting the anterior segment of the eye and causing systemic malformations, and follows an autosomal-dominant inheritance pattern. The aim of the present study was to identify the underlying cause of ARS in a Chinese family. Genomic DNA was extracted from the peripheral blood of the subjects from a family with ARS. The pathogenic variant was identified by targeted next-generation sequencing and confirmed by Sanger sequencing. A novel heterozygous mutation of the forkhead box (FOX)C1 gene (c.1494delG, p.G499Afs*20) was detected in all affected members of the family, while no mutation was identified in the unaffected members or in the 150 normal controls. The affected members exhibited typical ocular and craniofacial anomalies. The results of the present study demonstrated that a novel deletion in exon 1 of the FOXC1 gene caused ARS in this Chinese family.

A novel mutation in the VHL gene in a Chinese family with von Hippel-Lindau disease.

BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited cancer syndrome, and VHL is identified as a tumor suppressor gene. The main objective of this study was to identify disease-causing mutations in a Chinese family affected with VHL disease. METHODS: Genomic DNA was extracted from peripheral blood from a Chinese family with VHL. A predicted pathogenic variant was identified by targeted exome capture technology and next-generation sequencing. RESULTS: A novel heterozygous mutation (c.349 T > A, p.W117R) was detected in affected family members. No mutation was detected in unaffected family members or in the 150 normal controls. The mutation segregated with the disease phenotype throughout three generations. Histopathological examination revealed the characteristics of hemangioblastoma. CONCLUSIONS: A novel W117R was detected in the VHL gene that caused retinal hemangioblastomas in affected members of a Chinese family.

Fate of Liposomes in the Presence of Phospholipase C and D: From Atomic to Supramolecular Lipid Arrangement.

Understanding the origins of lipid membrane bilayer rearrangement in response to external stimuli is an essential component of cell biology and the bottom-up design of liposomes for biomedical applications. The enzymes phospholipase C and D (PLC and PLD) both cleave the phosphorus-oxygen bonds of phosphate esters in phosphatidylcholine (PC) lipids. The atomic position of this hydrolysis reaction has huge implications for the stability of PC-containing self-assembled structures, such as the cell wall and lipid-based vesicle drug delivery vectors. While PLC converts PC to diacylglycerol (DAG), the interaction of PC with PLD produces phosphatidic acid (PA). Here we present a combination of small-angle scattering data and all-atom molecular dynamics simulations, providing insights into the effects of atomic-scale reorganization on the supramolecular assembly of PC membrane bilayers upon enzyme-mediated incorporation of DAG or PA. We observed that PC liposomes completely disintegrate in the presence of PLC, as conversion of PC to DAG progresses. At lower concentrations, DAG molecules within fluid PC bilayers form hydrogen bonds with backbone carbonyl oxygens in neighboring PC molecules and burrow into the hydrophobic region. This leads initially to membrane thinning followed by a swelling of the lamellar phase with increased DAG. At higher DAG concentrations, localized membrane tension causes a change in lipid phase from lamellar to the hexagonal and micellar cubic phases. Molecular dynamics simulations show that this destabilization is also caused in part by the decreased ability of DAG-containing PC membranes to coordinate sodium ions. Conversely, PLD-treated PC liposomes remain stable up to extremely high conversions to PA. Here, the negatively charged PA headgroup attracts significant amounts of sodium ions from the bulk solution to the membrane surface, leading to a swelling of the coordinated water layer. These findings are a vital step toward a fundamental understanding of the degradation behavior of PC lipid membranes in the presence of these clinically relevant enzymes, and toward the rational design of diagnostic and drug delivery technologies for phospholipase-dysregulation-based diseases.

Fast Optical Chemical and Structural Classification of RNA.

As more biological activities of ribonucleic acids continue to emerge, the development of efficient analytical tools for RNA identification and characterization is necessary to acquire an in-depth understanding of their functions and chemical properties. Herein, we demonstrate the capacity of label-free direct surface-enhanced Raman scattering (SERS) analysis to access highly specific structural information on RNAs at the ultrasensitive level. This includes the recognition of distinctive vibrational features of RNAs organized into a variety of conformations (micro-, fully complementary duplex-, small interfering- and short hairpin-RNAs) or characterized by subtle chemical differences (single-base variances, nucleobase modifications and backbone composition). This method represents a key advance in the ribonucleic acid analysis and will have a direct impact in a wide range of different fields, including medical diagnosis, drug design, and biotechnology, by enabling the rapid, high-throughput, simple, and low-cost identification and classification of structurally similar RNAs.

Ultrasensitive Direct Quantification of Nucleobase Modifications in DNA by Surface-Enhanced Raman Scattering: The Case of Cytosine.

Recognition of chemical modifications in canonical nucleobases of nucleic acids is of key importance since such modified variants act as different genetic encoders, introducing variability in the biological information contained in DNA. Herein, we demonstrate the feasibility of direct SERS in combination with chemometrics and microfluidics for the identification and relative quantification of 4 different cytosine modifications in both single- and double-stranded DNA. The minute amount of DNA required per measurement, in the sub-nanogram regime, removes the necessity of pre-amplification or enrichment steps (which are also potential sources of artificial DNA damages). These findings show great potentials for the development of fast, low-cost and high-throughput screening analytical devices capable of detecting known and unknown modifications in nucleic acids (DNA and RNA) opening new windows of activity in several fields such as biology, medicine and forensic sciences.

Fibres and cellular structures preserved in 75-million-year-old dinosaur specimens.

Exceptionally preserved organic remains are known throughout the vertebrate fossil record, and recently, evidence has emerged that such soft tissue might contain original components. We examined samples from eight Cretaceous dinosaur bones using nano-analytical techniques; the bones are not exceptionally preserved and show no external indication of soft tissue. In one sample, we observe structures consistent with endogenous collagen fibre remains displaying ∼ 67 nm banding, indicating the possible preservation of the original quaternary structure. Using ToF-SIMS, we identify amino-acid fragments typical of collagen fibrils. Furthermore, we observe structures consistent with putative erythrocyte remains that exhibit mass spectra similar to emu whole blood. Using advanced material characterization approaches, we find that these putative biological structures can be well preserved over geological timescales, and their preservation is more common than previously thought. The preservation of protein over geological timescales offers the opportunity to investigate relationships, physiology and behaviour of long extinct animals.

Revealing DNA interactions with exogenous agents by surface-enhanced Raman scattering.

The standard protocols for DNA analysis largely involve polymerase chain reaction (PCR). However, DNA structures bound to chemical agents cannot be PCR-amplified, and therefore any sequence changes induced by external agents may be neglected. Thus, the development of analytical tools capable of characterizing the biochemical mechanisms associated with chemically induced DNA damage is demanded for the rational design of more effective chemotherapy drugs, understanding the mode of actions of carcinogenic chemicals, and monitoring the genotypic toxicology of environments. Here we report a fast, high-throughput, low-cost method for the characterization and quantitative recognition of DNA interactions with exogenous agents based on surface-enhanced Raman scattering spectroscopy. As representative chemical agents, we selected a chemotherapeutic drug (cisplatin) which forms covalent adducts with DNA, a duplex intercalating agent (methylene blue), and a cytotoxic metal ion (Hg(II)) which inserts into T:T mismatches. Rich structural information on the DNA complex architecture and properties is provided by the unique changes of their SERS spectra, which also offer an efficient analytical tool to quantify the extent of such binding.

Identification of intracellular gold nanoparticles using surface-enhanced Raman scattering.

The identification of intracellular distributions of noble metal nanoparticles is of great utility for many biomedical applications. We present an effective method to distinguish intracellular from extracellular nanoparticles by selectively quenching the SERS signals from dye molecules adsorbed onto star-shaped gold nanoparticles that have not been internalized by cells.

Synthesis and NIR optical properties of hollow gold nanospheres with LSPR greater than one micrometer.

Optical analysis in the near infrared region is of significant biological importance due to better tissue penetration and reduced autofluorescence. In this work, an improved synthesis of hollow gold nanospheres (HGNs), which provides a tunable localized surface plasmon resonance (LSPR) from 610 nm up to 1320 nm, is demonstrated. The scattering properties of these nanoparticles are shown using surface enhanced Raman scattering (SERS) at 1064 nm excitation wavelength and are compared to citrate reduced gold and silver nanoparticles of similar physical sizes and surface properties. After the addition of salts, a strong signal was observed from hollow gold with a LSPR of 650 nm and a weaker, yet observable, signal from HGNs with a LSPR of 775 nm. However, no obvious signals were observed in the case of standard citrate reduced gold, silver or HGNs with a LSPR of 1080 nm. The absorption properties of HGNs were investigated by monitoring their photothermal activity. In this case, different nanoparticle suspensions including citrate reduced gold, silver, and HGNs were illuminated by a continuous laser at 785 nm excitation wavelength and the absorption efficiency of HGNs with a LSPR of 775 nm was calculated to be 0.81% which is more than 5 times higher than the absorption efficiency of citrate reduced gold nanoparticles under similar conditions.

Ocular siderosis.

Ocular siderosis refers to intraocular iron deposition in ocular tissues caused by the long-time retention of penetrating iron-containing foreign bodies, commonly leading to a series of characteristic alterations and severe disorder of visual function. Ocular siderosis, rarely seen in the clinic, can cause irreversible retinal injuries and visual function damage and can even affect the appearance of the eyeballs. These effects significantly decrease the quality of life of patients and lead to poor prognosis. This study summarizes ocular siderosis with respect to pathogenesis, clinical manifestations, diagnosis, treatment, and sequelae, with the aim of assisting clinicians in the diagnosis and treatment of ocular siderosis.

Tracking bisphosphonates through a 20 mm thick porcine tissue by using surface-enhanced spatially offset Raman spectroscopy.

Track it down: A recognized surface-enhanced Raman scattering (SERS) nanotag signal was monitored from a thin, dispersed layer of bisphosphonate-functionalized nanotags on a bone sample, through a 20 mm thick specimen of porcine muscle tissue by surface-enhanced spatial offset Raman spectroscopy (SESORS; see picture). The result demonstrates the great potential for non-invasive in vivo bisphosphonate drug tracking.

Enhancing the SERS properties of nanoworms by matrix formation.

A highly SERS-active substrate was fabricated by trapping gold "nanoworms" on commercially available filter membranes providing significant enhancement of the Raman signal as a result of the remarkable electromagnetic couplings induced by the dense packing. The resultant substrate provides a simple and cost-effective porous SERS surface for use and quantitative analytical procedures.