De novo assembled mitogenome analysis of Trichuris trichiura from Korean individuals using nanopore-based long-read sequencing technology.

Knowledge about mitogenomes has been proven to be essential in human parasite diagnostics and understanding of their diversity. However, the lack of substantial data for comparative analysis is still a challenge in Trichuris trichiura research. To provide high quality mitogenomes, we utilized long-read sequencing technology of Oxford Nanopore Technologies (ONT) to better resolve repetitive regions and to construct de novo mitogenome assembly minimizing reference biases. In this study, we got three de novo assembled mitogenomes of T. trichiura isolated from Korean individuals. These circular complete mitogenomes of T. trichiura are 14,508 bp, 14,441 bp, and 14,440 bp in length. A total of 37 predicted genes were identified consisting of 13 protein-coding genes (PCGs), 22 transfer RNA (tRNAs) genes, two ribosomal RNA (rRNA) genes (rrnS and rrnL), and two non-coding regions. Interestingly, the assembled mitogenome has up to six times longer AT-rich regions than previous reference sequences, thus proving the advantage of long-read sequencing in resolving unreported non-coding regions. Furthermore, variant detection and phylogenetic analysis using concatenated protein coding genes, cox1, rrnL, and nd1 genes confirmed the distinct molecular identity of this newly assembled mitogenome while at the same time showing high genetic relationship with sequences from China or Tanzania. Our study provided a new set of reference mitogenome with better contiguity and resolved repetitive regions that could be used for meaningful phylogenetic analysis to further understand disease transmission and parasite biology.

In Vivo Electroporation Improves Retinal Delivery of Intravitreally Injected Exosomes.

Purpose: Mesenchymal stem cell (MSC)-derived exosomes are promising therapeutic agents and natural nanoscale delivery platforms for treating degenerative retinal diseases. This study investigated the effect of electroporation on the retinal delivery of intravitreally administered MSC-derived exosomes in a murine model. Methods: Exosomes isolated from adipose tissue-derived MSCs were stained with ExoGlow exosome-specific dye and administered to the right eyes of 40 Sprague-Dawley rats. Electroporation was performed in 20 rats immediately after intravitreal injection (electroporation group); 5 square pulses of 40 V/cm for 50 ms each with 950-ms intervals were administered. The remaining 20 rats were assigned to the no-electroporation group. The eyeballs were harvested 24 h later for evaluation. The total number of fluorescent particles per hyperfield was counted from the retinal flat mounts to quantify the retinal delivery of exosomes. Tissue damage after electroporation was evaluated using retinal histological sections and a terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end labeling (TUNEL) assay. Results: A significantly higher number of fluorescent particles per hyperfield were observed in the retinal flat mounts of the electroporation group compared with that in the no-electroporation group (599.0 ± 307.5 vs. 376.9 ± 175.4; P = 0.013). Retinal histological sections and TUNEL assays showed no signs of tissue damage after electroporation. Conclusions: In vivo electroporation can improve the retinal delivery of intravitreally injected exosomes.

Reserpine maintains photoreceptor survival in retinal ciliopathy by resolving proteostasis imbalance and ciliogenesis defects.

Ciliopathies manifest from sensory abnormalities to syndromic disorders with multi-organ pathologies, with retinal degeneration a highly penetrant phenotype. Photoreceptor cell death is a major cause of incurable blindness in retinal ciliopathies. To identify drug candidates to maintain photoreceptor survival, we performed an unbiased, high-throughput screening of over 6000 bioactive small molecules using retinal organoids differentiated from induced pluripotent stem cells (iPSC) of rd16 mouse, which is a model of Leber congenital amaurosis (LCA) type 10 caused by mutations in the cilia-centrosomal gene CEP290. We identified five non-toxic positive hits, including the lead molecule reserpine, which maintained photoreceptor development and survival in rd16 organoids. Reserpine also improved photoreceptors in retinal organoids derived from induced pluripotent stem cells of LCA10 patients and in rd16 mouse retina in vivo. Reserpine-treated patient organoids revealed modulation of signaling pathways related to cell survival/death, metabolism, and proteostasis. Further investigation uncovered dysregulation of autophagy associated with compromised primary cilium biogenesis in patient organoids and rd16 mouse retina. Reserpine partially restored the balance between autophagy and the ubiquitin-proteasome system at least in part by increasing the cargo adaptor p62, resulting in improved primary cilium assembly. Our study identifies effective drug candidates in preclinical studies of CEP290 retinal ciliopathies through cross-species drug discovery using iPSC-derived organoids, highlights the impact of proteostasis in the pathogenesis of ciliopathies, and provides new insights for treatments of retinal neurodegeneration.

Leber congenital amaurosis (LCA) is an inherited disease that affects the eyes and causes sight loss in early childhood, which generally gets worse over time. Individuals with this condition have genetic mutations that result in the death of light-sensitive cells, known as photoreceptors, in a region called the retina at the back of the eye. Patients carrying a genetic change in the gene CEP290 account for 20-25% of all LCA. At present, treatment options are only available for a limited number of patients with LCA. One option is to use small molecules as drugs that may target or bypass the faulty processes within the eye to help the photoreceptors survive in many different forms of LCA and other retinal diseases. However, over 90% of new drug candidates fail the first phase of clinical trials for human diseases. This in part due to the candidates having been developed using cell cultures or animal models that do not faithfully reflect how the human body works. Recent advances in cell and developmental biology are now enabling researchers to use stem cells derived from humans to grow retina tissues in a dish in the laboratory. These tissues, known as retinal organoids, behave in a more similar way to retinas in human eyes than those of traditional animal models. However, the methods for making and maintaining human retinal organoids are time-consuming and labor-intensive, which has so far limited their use in the search for new therapies. To address this challenge, Chen et al. developed a large-scale approach to grow retinal organoids from rd16 mutant mice stem cells (which are a good model for LCA caused by mutations to CEP290) and used the photoreceptors from these organoids to screen over 6,000 existing drugs for their ability to promote the survival of photoreceptors. The experiments found that the drug reserpine, which was previously approved to treat high blood pressure, also helped photoreceptors to survive in the diseased organoids. Reserpine also had a similar effect in retinal organoids derived from human patients with LCA and in the rd16 mice themselves. Further experiments suggest that reserpine may help patients with LCA by partially restoring a process by which the body destroys and recycles old and damaged proteins in the cells. The next steps following on from this work will be to perform further tests to demonstrate that this use of reserpine is safe to enter clinical trials as a treatment for LCA and other similar eye diseases.

Prevalence and Risk Factors of Intestinal Helminthiasis in Remote Mountainous Villages of Northern Lao PDR: A Cross-Sectional Study.

Helminth infections are prevalent in Lao People's Democratic Republic (Lao PDR). This study aimed at determining the prevalence and risk factors of intestinal helminthiasis in remote mountainous villages of northern Lao PDR. During the dry season in January 2017, a cross-sectional survey was conducted in 3 remote mountainous villages in Oudomxay province, Lao PDR. Villagers older than 18 years of age who agreed to submit stool samples or undergo an interview, were recruited. Stool samples from 198 individuals were examined by the Kato-Katz method, and a questionnaire surveyed 161 individuals among them. Univariable and multivariable logistic regression analyses were used to identify risk factors associated with the intestinal helminthiasis. An overall prevalence of intestinal helminthiasis was 75.8%. Hookworm infection was the most common (63.1%), followed by Opisthorchis viverrini/minute intestinal flukes (17.7%), Taenia spp. (15.2%), Trichuris trichiura (2.0%), Ascaris lumbricoides (1.5%), and Enterobius vermicularis (1.0%). Questionnaire analysis revealed sex (male) and absence of latrine to be significant risk factors for hookworm infection and consumption of raw meat for taeniasis. These results suggest that the mountainous area in northern Lao PDR has a different composition of helminth infections from other studies conducted in Lao PDR; a high prevalence of hookworm infection and taeniasis and low prevalence of T. trichiura and A. lumbricoides infections were observed. Also, liver flukes or intestinal flukes were similarly prevalent in the mountainous area.

Single Administration of a Biodegradable, Separable Microneedle Can Substitute for Repeated Application of Eyedrops in the Treatment of Infectious Keratitis.

Infectious keratitis is mainly treated with topical antibiotics. To achieve and maintain the required therapeutic concentration in the cornea where the tear fluid continuously rinses the surface, the antibiotics must be frequently applied, even while the patient is sleeping, and oral medication is sometimes required. However, the inevitably poor compliance and avascular nature of the cornea decrease drug bioavailability. In this study, a single microneedle (MN) is injected into the cornea to substitute for the repeated application of eyedrops in the treatment of infectious keratitis. After comparing the mechanical integrity and drug release profiles of three different drug-tips, the drug-tip with the "high" drug concentration that releases 12.5 ng drug within 3 days is applied to a cornea to evaluate the transferability and in vivo drug release. In the treatment of infectious keratitis with repeated application of eyedrops for six consecutive days, a single MN injection is substituted for the initial 3 days of eyedrop applications. The progression remains similarly attenuated after 3 days without eyedrops, and comparable efficacy is achieved on day 6 when combined with delayed eyedrop treatment from day 3. Thus, the single administration of a biodegradable MN can substitute for the repeated application of eyedrops in the treatment of infectious keratitis.

Importance of extracutaneous organ involvement in determining the clinical severity and prognosis of incontinentia pigmenti caused by mutations in the IKBKG gene.

Incontinentia pigmenti (IP) is a rare X-linked skin disease caused by mutations in the IKBKG gene, which is required for activation of the nuclear factor-kappa B signalling pathway. Multiple systems can be affected with highly variable phenotypic expressivity. We aimed to clarify the clinical characteristics observed in molecularly confirmed Korean IP patients. The medical records of 25 females confirmed as IP by molecular genetic analysis were retrospectively reviewed. The phenotypic score of extracutaneous manifestations was calculated to assess the disease severity. The IKBKG gene partial deletion or intragenic mutations were investigated using long-range PCR, multiplex ligation-dependent probe amplification and direct sequencing methods. Among the 25 individuals, 18 (72%) were sporadic cases. All patients showed typical skin manifestations at birth or during the neonatal period. Extracutaneous findings were noted in 17 (68%) patients; ocular manifestations (28%), neurological abnormalities (28%), hair abnormalities (20%), dental anomalies (12%), nail dystrophy (8%). The common exon 4-10 IKBKG deletion was observed in 20 (80%) patients. In addition, five intragenic sequence variants were identified, including three novel variants. The phenotype scores were highly variable, ranging from abnormal skin pigmentation only to one or more extracutaneous features, although no significant difference was observed for each clinical characteristic between the group with sequence variants and that with common large deletion. Our cohort with IP showed heterogeneity of extracutaneous manifestations and high incidence of sporadic cases. Long-term monitoring with multidisciplinary management is essential for evaluating the clinical status, providing adequate genetic counselling and understanding the genotype-phenotype correlation in IP.

A mouse model of retinal hypoperfusion injury induced by unilateral common carotid artery occlusion.

Retina, one of the highest oxygen demanding tissues, is vulnerable to vascular insufficiencies, and various ocular vascular disorders can cause chronic retinal ischemia. To investigate the pathophysiology, rodent models developed by bilateral common carotid artery occlusion (BCCAO) have been utilized. However, mice lack posterior communicating arteries in the circle of Willis and cannot endure the brain ischemia induced by the bilateral occlusion. A mouse model to better reflect the localized ischemic stress in the retina without affecting the brain is still needed. Here, we established a mouse model of ischemic injury by permanent unilateral common carotid artery occlusion (UCCAO). Adult male mice were subjected to UCCAO, and changes in the ipsilateral retina were examined in comparison with the contralateral retina. Delayed perfusion was observed in the ipsilateral retina right after the occlusion and was not recovered later on. Common features of retinal ischemia were observed: hypoxia-inducible factor (HIF) stabilization; upregulation of hypoxia-responsive genes; altered levels of cytokines and chemokines. Activation of astrocytes and Müller cells in the inner retina was detected at day 2, and thinning of the inner retinal layer became significant at week 10. Together, our model can simulate retinal ischemia with morphological and molecular changes. It can be utilized to investigate pathophysiology of ischemic retinopathies.

Prevalence of Toxocariasis and Its Risk Factors in Patients with Eosinophilia in Korea.

Eosinophilia occurs commonly in many diseases including allergic diseases and helminthic infections. Toxocariasis has been suggested as one cause of eosinophilia. The present study was undertaken to examine the prevalence of toxocariasis in patients with eosinophilia and to identify the risk factors for toxocariasis. This prospective cohort study recruited a total of 81 patients with eosinophilia (34 males and 47 females) who visited the outpatient clinic at Seoul National University Hospital from January 2017 to February 2018 and agreed to participate in this study. The prevalence of toxocariasis was examined by T. canis-specific ELISA, and the various risk factors for toxocariasis were evaluated by a questionnaire survey. Among 81 patients with eosinophilia, 18 were positive for anti-T. canis antibodies (22.2%); 88.9% were male (16/18) and 11.1% were female (2/18). Multivariate statistical analysis revealed that males (OR 21.876, 95% CI: 1.667-287.144) with a history of consuming the raw meat or livers of animals (OR 5.899, 95% CI: 1.004-34.669) and a heavy alcohol-drinking habit (OR 8.767, 95% CI: 1.018-75.497) were at higher risk of toxocariasis in patients with eosinophilia. Toxocariasis should be considered a potential cause of eosinophilia when the patient has a history of eating the raw meat or livers of animals in Korea. A single course of albendazole is recommended to reduce the migration of Toxocara larvae in serologically positive cases with eosinophilia.

Case Report of Urinary Schistosomiasis in a Returned Traveler in Korea.

A 23-year-old Korean woman with a residence history in Kenya and Malawi for about 2 years presented with gross hematuria for 1 month. Blood tests were within normal range except eosinophilia. Asymmetrically diffuse wall thickening and calcification were observed at the urinary bladder on CT. Multiple erythematous nodular lesions were observed in the cystoscopy and transurethral resection was done. Numerous eggs of Schistosoma haematobium with granulomatous inflammation were observed in the submucosal layer of the bladder. The patient was diagnosed with schistosomiasis-related cystitis and treated with praziquantel (40 mg/kg/day) twice before and after transurethral resection. This case suggests that S. haematobium infection should be considered as a cause of hematuria in Korea when the patient had a history of traveling endemic areas of schistosomiasis.

Intracorneal injection of a detachable hybrid microneedle for sustained drug delivery.

There are increasing demands for long-term and controlled corneal drug delivery to treat various ocular diseases. Although biodegradable ocular inserts or contact lenses have been developed, the invasiveness and inefficiency of the approaches still need to be improved. Microneedle (MN) technology can deliver therapeutic molecules to the eye in a minimally invasive manner. However, the current ocular MN technology is limited to either short-term corneal drug delivery or retinal drug delivery by suprachoroidal injection. For long-term and minimally invasive corneal drug delivery, we have developed a detachable biodegradable MN that can be delivered to the inside of the cornea for sustained drug release. The detachable and biodegradable MN is a hybrid MN consisting of a drug-loaded biodegradable tip and a supporting base. The hybrid MN can be applied to the cornea by impact insertion, and it leaves only the drug-loaded biodegradable tip within the corneal tissue so that it can release the drug for a certain period. By concentration-controlled molding, the dimension of drug-loaded MN tips was precisely controlled and their detachability was optimized. The detachable tip and a supporting base were assembled to form a hybrid MN by pressure-assisted transfer molding. We carefully optimized the dimension of the drug-tip, injection dwell time, and insertion depth to achieve effective intracorneal injection of the drug-tip. The detachable hybrid MN was applied to an Acanthamoeba keratitis model wherein a biodegradable drug-tip was successfully delivered to the inside of the mouse cornea in vivo. Follow-up of the MN-treated cases for 7 days confirmed the therapeutic efficacy of the detachable biodegradable MN tips. STATEMENT OF SIGNIFICANCE: For the treatment of infectious diseases in the cornea, such as keratitis, eye drops need to be applied topically every hour for a couple of days. This is extremely uncomfortable, and poor compliance to such tightly scheduled drug administration can result in permanent scar formation in the cornea. In this work, we demonstrate a simple and rapid injection of biodegradable microneedle tips in the corneal tissue wherein the tips can deliver antibacterial drugs for 4 days to treat keratitis. Unlike other patch-style microneedle technologies, this approach allows for insertion depth-controlled and highly localized injection of detachable individual microneedle tips to the diseased tissue for sustained drug delivery. This overcomes the limitations of patch-style microneedles such as short-term drug delivery and unnecessary blockage of tissue.

Comparison of ELISA and Urine Microscopy for Diagnosis of Schistosoma haematobium Infection.

BACKGROUND: Schistosoma haematobium which causes urogenital schistosomiasis (UGS) is highly prevalent in African countries. Urine microscopy (UM) is the first-line diagnostic method of UGS. Enzyme-linked immunosorbent assay (ELISA) is a common method for screening many parasite infections primarily or alternatively. The present study established an in-house diagnostic system by ELISA and evaluated its diagnostic efficacy in comparison with UM for screening UGS in White Nile State, Republic of Sudan, 2011-2013. METHODS: A total of 490 participants were screened by UM or ELISA, and 149 by both. The in-house ELISA system was established employing soluble egg antigen of S. haematobium and the cut-off absorbance was set at 0.270. RESULTS: Of the 149 subjects, 58 participants (38.9%) were positive by UM, 119 (79.9%) were positive by ELISA and 82 (55.0%) showed consistently positive or negative results by both methods. The diagnostic sensitivity of ELISA was 94.8% and specificity was 29.7% based on UM results. The ELISA positive serum samples also cross-reacted with egg antigens of Schistosoma mansoni and Schistosoma japonicum. CONCLUSION: We have established in-house ELISA for screening serum immunoglobulin (Ig) G antibodies by employing soluble egg antigen of S. haematobium for diagnosis of UGS with 94.8% sensitivity and 29.7% specificity. The ELISA system can supplement the conventional diagnosis by UM.

Investigation of tissue cysts in the retina in a mouse model of ocular toxoplasmosis: distribution and interaction with glial cells.

The conversion of tachyzoites into bradyzoites is a way for Toxoplasma gondii to establish a chronic and asymptomatic infection and achieve lifelong persistence in the host. The bradyzoites form tissue cysts in the retina, but not much is known about the horizontal distribution of the cysts or their interactions with glial cells in the retina. A chronic ocular toxoplasmosis model was induced by per oral administration of T. gondii Me49 strain cysts to BALB/c mice. Two months after the infection, retinas were flat-mounted and immunostained to detect cysts, ganglion cells, Müller cells, astrocytes, and microglial cells, followed by observation under fluorescence and confocal microscope. The horizontal distribution showed a rather clustered pattern, but the clusters were not restricted to certain location of the retina. Axial distribution was confined to the inner retina, mostly in ganglion cell layer or the inner plexiform layer. Both ganglion cells, a type of retinal neurons, and Müller cells, predominant retinal glial cells, could harbor cysts. The cysts were spatially separated from astrocytes, the most abundant glial cells in the ganglion cell layer, while close spatial distribution of microglial cells was observed in two thirds of retinal cysts. In this study, we demonstrated that the retinal cysts were not evenly distributed horizontally and were confined to the inner retina axially. Both neurons and one type of glial cells could harbor cysts, and topographic analysis of other glial cells suggests role of microglial cells in chronic ocular toxoplasmosis.

Mesenchymal Stromal Cells Inhibit Inflammatory Lymphangiogenesis in the Cornea by Suppressing Macrophage in a TSG-6-Dependent Manner.

The cornea is a transparent tissue devoid of blood and lymphatic vessels. However, various inflammatory conditions can cause hemangiogenesis and lymphangiogenesis in the cornea, compromising transparency and visual acuity. Mesenchymal stem/stromal cells (MSCs) have therapeutic potentials in a variety of diseases because of anti-inflammatory properties. Herein, we investigated the effects of MSCs on corneal angiogenesis using a model of suture-induced inflammatory corneal neovascularization. Data demonstrated that an intravenous administration of MSCs suppressed corneal inflammation and neovascularization, inhibiting both hemangiogenesis and lymphangiogenesis. MSCs reduced the levels of vascular endothelial growth factor (VEGF)-C, VEGF-D, Tek, MRC1, and MRC2 in the cornea, which are expressed by pro-angiogenic macrophages. Moreover, the number of CD11b+ monocytes/macrophages in the cornea, spleen, peripheral blood, and draining lymph nodes was decreased by MSCs. Depletion of circulating CD11b+ monocytes by blocking antibodies replicated the effects of MSCs. Importantly, knockdown of tumor necrosis factor alpha (TNF-α)-stimulated gene/protein 6 (TSG-6) in MSCs abrogated the effects of MSCs in inhibiting corneal hemangiogenesis and lymphangiogenesis and monocyte/macrophage infiltration. Together, the results suggest that MSCs inhibit inflammatory neovascularization in the cornea by suppressing pro-angiogenic monocyte/macrophage recruitment in a TSG-6-dependent manner.

Application of a loop-mediated isothermal amplification (LAMP) assay targeting cox1 gene for the detection of Clonorchis sinensis in human fecal samples.

BACKGROUND: Clonorchiasis is prevalent in the Far East, and a major health problem in endemic areas. Infected persons may experience, if not treated, serious complications such as bile stone formation, pyogenic cholangitis, and even cholangiocarcinoma. Early diagnosis and treatment are important to prevent serious complications and, therefore, the simple and reliable diagnostic method is necessary to control clonorchiasis in endemic areas, where resources for the diagnosis are limited. METHODOLOGY/PRINCIPLE FINDINGS: The loop-mediated isothermal amplification (LAMP) assay has been applied for the detection of Clonorchis sinensis DNA. Six primers targeting eight locations on the cytochrome c oxidase subunit 1 gene of C. sinensis were designed for species-specific amplification using the LAMP assay. The LAMP assay was sensitive enough to detect as little as 100 fg of C. sinensis genomic DNA and the detection limit in 100 mg of stool was as low as one egg. The assay was highly specific because no cross-reactivity was observed with the DNA of other helminths, protozoa or Escherichia coli. Then, LAMP assay was applied to human fecal samples collected from an endemic area of clonorchiasis in Korea. Using samples showing consistent results by both Kato-Katz method and real-time PCR as reference standards, the LAMP assay showed 97.1% (95% CI, 90.1-99.2) of sensitivity and 100% (95% CI, 92.9-100) of specificity. In stool samples with more than 100 eggs per gram of feces, the sensitivity achieved 100%. CONCLUSIONS: To detect C. sinensis in human fecal samples, the LAMP assay was applied and achieved high sensitivity and specificity. The LAMP assay can be utilized in field laboratories as a powerful tool for diagnosis and epidemiological survey of clonorchiasis.

In Vivo Photoacoustic Imaging of Anterior Ocular Vasculature: A Random Sample Consensus Approach.

Visualizing ocular vasculature is important in clinical ophthalmology because ocular circulation abnormalities are early signs of ocular diseases. Photoacoustic microscopy (PAM) images the ocular vasculature without using exogenous contrast agents, avoiding associated side effects. Moreover, 3D PAM images can be useful in understanding vessel-related eye disease. However, the complex structure of the multi-layered vessels still present challenges in evaluating ocular vasculature. In this study, we demonstrate a new method to evaluate blood circulation in the eye by combining in vivo PAM imaging and an ocular surface estimation method based on a machine learning algorithm: a random sample consensus algorithm. By using the developed estimation method, we were able to visualize the PA ocular vascular image intuitively and demonstrate layer-by-layer analysis of injured ocular vasculature. We believe that our method can provide more accurate evaluations of the eye circulation in ophthalmic applications.

Disruption of outer blood-retinal barrier by Toxoplasma gondii-infected monocytes is mediated by paracrinely activated FAK signaling.

Ocular toxoplasmosis is mediated by monocytes infected with Toxoplasma gondii that are disseminated to target organs. Although infected monocytes can easily access to outer blood-retinal barrier due to leaky choroidal vasculatures, not much is known about the effect of T. gondii-infected monocytes on outer blood-retinal barrier. We prepared human monocytes, THP-1, infected with T. gondii and human retinal pigment epithelial cells, ARPE-19, grown on transwells as an in vitro model of outer blood-retinal barrier. Exposure to infected monocytes resulted in disruption of tight junction protein, ZO-1, and decrease in transepithelial electrical resistance of retinal pigment epithelium. Supernatants alone separated from infected monocytes also decreased transepithelial electrical resistance and disrupted tight junction protein. Further investigation revealed that the supernatants could activate focal adhesion kinase (FAK) signaling in retinal pigment epithelium and the disruption was attenuated by FAK inhibitor. The disrupted barrier was partly restored by blocking CXCL8, a FAK activating factor secreted by infected monocytes. In this study, we demonstrated that monocytes infected with T. gondii can disrupt outer blood-retinal barrier, which is mediated by paracrinely activated FAK signaling. FAK signaling can be a target of therapeutic approach to prevent negative influence of infected monocytes on outer blood-retinal barrier.

Intraocular application of gold nanodisks optically tuned for optical coherence tomography: inhibitory effect on retinal neovascularization without unbearable toxicity.

Bare gold nanospheres have been shown to have anti-angiogenic effects but are optically unfavorable because their resonant wavelength lies in the visible spectrum. Here, we design gold nanodisks with a higher scattering capability than gold nanorods and with a resonant wavelength at near-infrared region - the area where the source of light utilized by optical coherence tomography (OCT) lies. With a physical synthesis system, we then fabricate 160-nm-sized gold nanodisks exhibiting resonant wavelength at 830 nm. The synthesized nanoparticles were successfully visualized in in vivo OCT at concentrations as low as 1 pM. After demonstrating their binding ability to vascular endothelial growth factor (VEGF), we show that they suppress VEGF-induced migration of endothelial cells. Finally, we demonstrate that intravitreally injected gold nanodisks attenuate neovascularization of oxygen-induced retinopathy in mice, in a dose dependent manner, such that they are cleared from the vitreous within 2 weeks without histologic or electrophysiologic toxicity.

Effect of fronto-orbital advancement on astigmatism in patients with anterior plagiocephaly.

The purpose of this study was to determine the effect of unilateral fronto-orbital advancement (FOA) or bilateral FOA on ocular aspects of plagiocephaly. A retrospective review of ocular findings in 16 patients with plagiocephaly was performed. Patients were divided into 2 groups: 12 patients who underwent bilateral FOA (bFOA) and 4 patients who underwent unilateral FOA (uFOA), and ocular findings were compared. One-half of patients showed strabismus in both groups, and all had exotropia. Hypertropia was found only on the same side of the plagiocephaly in 17% of the bFOA group and 25% of the uFOA group. One-third of the patients in the bFOA group and one-half of patients in the uFOA group had oblique muscle dysfunction. In terms of astigmatism, the degree of with-the-rule astigmatism on the contralateral side was larger in the bFOA group compared to the uFOA group (p = 0.030). The degree of with-the-rule astigmatism was larger on the contralateral side than the ipsilateral side (p = 0.005) in the bFOA group. Patients with abnormalities in ductions/versions had larger astigmatism on the contralateral side than those without abnormalities in ductions/versions. In conclusion, bilateral FOA could induce unwanted outcomes of larger astigmatism on the contralateral side. Astigmatism should be carefully evaluated after bilateral FOA.