Transcriptome analysis reveals tissue-specific responses of Mytilus unguiculatus to Vibrio alginolyticus infection.

Mytilus unguiculatus is an important economic bivalve species with wide consumption and aquaculture value. Disease is one of the primary limiting factors in mussel aquaculture, thus understanding the response of different tissues of M. unguiculatus to pathogens is crucial for disease prevention and control. In this study, we investigated the physiological and transcriptomic responses of the gills, adductor muscle, and mantle of M. unguiculatus infected with Vibrio alginolyticus. The results showed that V. alginolyticus infection caused inflammation and tissue structure changes in the gill, adductor muscle and mantle of M. unguiculatus. Meanwhile, the activities of superoxide dismutase and catalase in the three tissues increased, while the total antioxidant capacity decreased, suggesting that M. unguiculatus have an activated defense mechanism against infection-induced oxidative stress, despite a compromised total antioxidant capacity. Transcriptomic studies reveal that infected M. unguiculatus exhibits upregulation of endocytosis, lysosome activity, cellular apoptosis, and immune-related signaling pathways, indicating that M. unguiculatus responds to pathogen invasion by upregulating efferocytosis. Compared with the gill and adductor muscle, the mantle had a higher level of mytimycin, mytilin and myticin, and the three tissues also increased the expression of mytimycin to cope with the invasion of pathogens. In addition, the analysis of genes related to taste transduction pathways and muscle contraction and relaxation found that after infection with V. alginolyticus, M. unguiculatus may reduce appetite by inhibiting taste transduction in the gill, while improving muscle contraction of the adductor muscle and keeping the shell closed, to resist further invasion of pathogens and reduce the risk of pathogen transmission in the population.

A case of endocardial dissection caused by Micra implantation.

BACKGROUND: Leadless pacemakers are a recent technological advancement. It has many advantages, but there are still a few serious complications. CASE PRESENTATION: This article reports the case of a patient with an endocardial tear and dissection caused by contact with the tip of the Micra cup during surgery and summarises the relevant data. CONCLUSIONS: This case report details the occurrence and management of the incident and provides some guidance for future clinical management.

Epicardial implantation of a lumenless active fixation lead in a neonate.

BACKGROUND: We present a case of epicardial pacemaker implantation in a low birth weight newborn using a lumenless active fixation lead. RESULTS: We found that superior pacing parameters can be obtained by implanting a lumenless active fixation lead into the epicardium, but more evidence is needed to support this hypothesis.

Peripapillary circulatory dysfunction precedes structural loss in treatment-naive diabetic retinopathy.

PURPOSE: The aim of this study was to compare the timing of peripapillary vascular damage between functional and structural parameters and examine their involvement with neurovascular coupling at different stages of diabetic retinopathy (DR). METHODS: One hundred ninety eyes of 143 patients with type 2 diabetes mellitus (DM) and 88 healthy control eyes were enrolled. Eyes of DM patients were divided into 3 stages with no diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). NPDR and PDR eyes were treatment-naive. OCT angiography was used to calculate radial peripapillary capillary (RPC)-flux index (FI) and RPC-perfusion density (PD). Spectral domain OCT was used to measure retinal nerve fiber layer (RNFL) thickness within the corresponding RPC areas. RESULTS: RPC-FI significantly decreased in NDR eyes compared to control eyes and thereafter remained unchanged among DM (NDR, NPDR, and PDR) eyes. In contrast, RPC-PD stayed unaltered between control and NDR eyes and significantly decreased in NPDR followed by PDR eyes at similar levels. From control to NPDR eyes, RNFL thickness showed positive correlations with both RPC-FI and RPC-PD, indicative of functional and structural neurovascular coupling. These vascular parameters were also correlated with each other in control and NPDR eyes but not NDR eyes, consistent with the difference in the timing of vascular damage between functional and structural parameters. CONCLUSIONS: Circulatory dysfunction preceded structural loss while maintaining peripapillary neurovascular coupling during progression of DR stages. RPC-FI would likely be more sensitive than RPC-PD in detecting early vascular damage in DR.

A propensity score matched comparison of blood pressure lowering in essential hypertension patients treated with antihypertensive Chinese herbal Medicine: comparing the real-world registry data vs. randomized controlled trial.

BACKGROUND: Randomized controlled trials have demonstrated that Songling Xuemaikang capsule (SXC) is effective in blood pressure (BP) lowering for essential hypertension. However, the effectiveness of SXC in real-world clinical practice remains unknown. We aimed to investigate whether the BP-lowering effectiveness of SXC in the real-world practice setting is comparable to the efficacy of the intervention in a randomized controlled trial. METHODS: We included 1325 patients treated with SXC monotherapy from a real-world registry and 300 from the SXC-BP trial. A propensity score matching (PSM) approach was used to select participants from the two cohorts. The primary outcome was a change in the office of BP from baseline to 8 weeks. RESULTS: After PSM, there were 552 patients for the comparative analysis. Clinically meaningful BP reductions were observed both in the real world and in the RCT cohorts after 8-week SXC treatment. The 8-week systolic/diastolic BP was 129.50/81.33 mm Hg vs. 134.97/84.14 mm Hg in the real-world population and the RCT population, respectively. The changes in systolic BP (15.82 ± 10.71 vs. 10.48 ± 10.24; P < .001), and diastolic BP (10.01 ± 7.73 vs. 7.75 ± 8.14; P = .001) from baseline to 8 weeks were significantly greater in the real-world population. CONCLUSION: The current comparison demonstrated that SXC monotherapy is at least as effective in real-world settings as within the randomized controlled trial for BP lowering in patients with grade 1 hypertension.

Genetic Diversity, Population Structure, and Environmental Adaptation Signatures of Chinese Coastal Hard-Shell Mussel Mytilus coruscus Revealed by Whole-Genome Sequencing.

The hard-shell mussel (Mytilus coruscus) is widespread in the temperate coastal areas of the northwest Pacific and holds a significant position in the shellfish aquaculture market in China. However, the natural resources of this species have been declining, and population genetic studies of M. coruscus are also lacking. In this study, we conducted whole-genome resequencing (WGR) of M. coruscus from eight different latitudes along the Chinese coast and identified a total of 25,859,986 single nucleotide polymorphism (SNP) markers. Our findings indicated that the genetic diversity of M. coruscus from the Zhoushan region was lower compared with populations from other regions. Furthermore, we observed that the evolutionary tree clustered into two primary branches, and the Zhangzhou (ZZ) population was in a separate branch. The ZZ population was partly isolated from populations in other regions, but the distribution of branches was not geographically homogeneous, and a nested pattern emerged, consistent with the population differentiation index (FST) results. To investigate the selection characteristics, we utilized the northern M. coruscus populations (Dalian and Qingdao) and the central populations (Zhoushan and Xiangshan) as reference populations and the southern ZZ population as the target population. Our selection scan analysis identified several genes associated with thermal responses, including Hsp70 and CYP450. These genes may play important roles in the adaptation of M. coruscus to different living environments. Overall, our study provides a comprehensive understanding of the genomic diversity of coastal M. coruscus in China and is a valuable resource for future studies on genetic breeding and the evolutionary adaptation of this species.

An Interleukin-17 Isoform from Thick Shell Mussel Mytilus coruscus Serves as a Mediator of Inflammatory Response.

The inflammatory cytokine interleukin-17 (IL17) plays an important role in innate immunity by binding to its receptors (IL17Rs) to activate immune defense signals. To date, information on members of the IL17 family is still very limited in molluscan species. Here, a novel member of the IL17 family was identified and characterized from thick shell mussel Mytilus coruscus, and this gene was designated as McIL17-1 by predicting structural domains and phylogenetic analysis. McIL17-1 transcripts existed in all examined tissues with high expression levels in gills, hemocytes and digestive glands. After the stimuli of different pathogen associated molecular patterns (PAMPs) for 72 h, transcriptional expression of McIL17-1 was significantly upregulated, except for poly I:C stimulation. Cytoplasm localization of McIL17-1 was shown in HEK293T cells by fluorescence microscopy. Further, in vivo and in vitro assays were performed to evaluate the potential function of McIL17-1 played in immune response. McIL17-1 was either knocked down or overexpressed in vivo through RNA inference (RNAi) and recombinant protein injection, respectively. With the infection of living Vibrio alginolyticus, a high mortality rate was exhibited in the McIL17-1 overexpressed group compared to the control group, while a lower mortality rate was observed in the McIL17-1 knocked down group than control group. In vitro, the flow cytometric analysis showed that the apoptosis rate of McIL17-1 inhibited hemocytes was significantly lower than that of the control group after lipopolysaccharide stimulation. These results collectively suggested that the newly identified IL17 isoform is involved in the inflammatory response to bacterial infection in M. coruscus.

Spatially variant deblur and image enhancement in a single multimode fiber imaged by deep learning.

A single multimode fiber has been applied in minimally invasive endoscopy with wavefront shaping for biological research such as brain imaging. Most of the fibers, such as step-index and graded-index multimode fibers, give rise to spatially variant blur due to limits on the numerical aperture and collection efficiency. Routines to solve this problem are based on iterative algorithms, which are often slow and computer-intense. We developed a method to synthesize datasets for driving a deep learning network to deblur and denoise the spatially variant degraded image. This approach is fast (5 ms), up to three orders of magnitude faster than the iterative way. Furthermore, our method can be applied to different types of fiber endoscopy, and two types of fiber are tested here. The performance is verified on fluorescence beads and three kinds of biological tissue sections in the experiment, demonstrating effectiveness in image enhancement.

Cholinergic Elicitation Prevents Ventricular Remodeling via Alleviations of Myocardial Mitochondrial Injury Linked to Inflammation in Ischemia-Induced Chronic Heart Failure Rats.

BACKGROUND: Cholinergic anti-inflammatory pathway (CAP) is implicated in cardioprotection in chronic heart failure (CHF) by downregulating inflammation response. Mitochondrial injuries play an important role in ventricular remodeling of the CHF process. Herein, we aim to investigate whether CAP elicitation prevents ventricular remodeling in CHF by protecting myocardial mitochondrial injuries and its underlying mechanisms. METHODS AND RESULTS: CHF models were established by ligation of anterior descending artery for 5 weeks. Postoperative survival rats were assigned into 5 groups: the sham group (sham, n = 10), CHF group (CHF, n = 11), Vag group (CHF+vagotomy, n = 10), PNU group (CHF+PNU-282987 for 4 weeks, n = 11), and Vag+PNU group (CHF+vagotomy+PNU-282987 for 4 weeks, n = 10). The antiventricular remodeling effect of cholinergic elicitation was evaluated in vivo, and H9C2 cells were selected for the TNF-α gradient stimulation experiment in vitro. In vivo, CAP agitated by PNU-282987 alleviated the left ventricular dysfunction and inhibited the energy metabolism remodeling. Further, cholinergic elicitation increased myocardium ATP levels and reduced systemic inflammation. CAP induction alleviates macrophage infiltration and cardiac fibrosis, of which the effect is counteracted by vagotomy. Myocardial mitochondrial injuries were ameliorated by CAP activation, including the reserved ultrastructural integrity, declining ROS overload, reduced myocardial apoptosis, and enhanced mitochondrial fusion. In vitro, TNF-α intervention significantly exacerbated the mitochondrial damage in H9C2 cells. CONCLUSION: CAP elicitation effectively improves ischemic ventricular remodeling by suppressing systemic and cardiac inflammatory response, attenuating cardiac fibrosis and potentially alleviating the mitochondrial dysfunction linked to hyperinflammation reaction.

FGF2-induced STAT3 activation regulates pathologic neovascularization.

Cell-autonomous endothelial cell (EC) fibroblast growth factor receptor (FGFR) signaling through FGFR1/2 is essential for injury-induced wound vascularization and pathologic neovascularization as in blinding eye diseases such as age-related macular degeneration. Which FGF ligand(s) is critical in regulating angiogenesis is unknown. Utilizing ex vivo models of choroidal endothelial sprouting and in vivo models of choroidal neovascularization (CNV), we demonstrate here that only FGF2 is the essential ligand. Though FGF-FGFR signaling can activate multiple intracellular signaling pathways, we show that FGF2 regulates pathogenic angiogenesis via STAT3 activation. The identification of FGF2 as a critical mediator in aberrant neovascularization provides a new opportunity for developing multi-target therapies in blinding eye diseases especially given the limitations of anti-VEGF monotherapy.

Disrupted cholesterol metabolism promotes age-related photoreceptor neurodegeneration.

Photoreceptors have high intrinsic metabolic demand and are exquisitely sensitive to metabolic perturbation. In addition, they shed a large portion of their outer segment lipid membranes in a circadian manner, increasing the metabolic burden on the outer retina associated with the resynthesis of cell membranes and disposal of the cellular cargo. Here, we demonstrate that deletion of both ABCA1 and ABCG1 in rod photoreceptors leads to age-related accumulation of cholesterol metabolites in the outer retina, photoreceptor dysfunction, degeneration of rod outer segments, and ultimately blindness. A high-fat diet significantly accelerates rod neurodegeneration and vision loss, further highlighting the role of lipid homeostasis in regulating photoreceptor neurodegeneration and vision.

Amelioration of endotoxin-induced uveitis treated with the sea urchin pigment echinochrome in rats.

PURPOSE: Echinochrome is a pigment present in the shells and spines of sea urchins. It has been reported to have several biologic protective effects, including in experimental models of myocardial ischemia/reperfusion injury, for which the proposed mechanisms are scavenging reactive oxygen species (ROS) and chelating iron. Endotoxin-induced uveitis (EIU) is an animal model of acute anterior segment intraocular inflammation that is induced by the injection of lipopolysaccharide (LPS). In this study, the therapeutic effect of echinochrome was examined in uveitis using the EIU model. METHODS: EIU was induced in Lewis rats via 200 µg subcutaneous injections of LPS from Escherichia coli. Echinochrome was administered intravenously in 10, 1, or 0.1 mg/kg doses suspended in PBS (controls were injected with PBS only). Twenty-four hours after LPS injection, the number of infiltrating cells and the protein concentration in aqueous humor were determined. Aqueous tumor necrosis factor α (TNF-α) concentration was quantified with enzyme-linked immunosorbent assay, eyes were stained with nuclear factor (NF) κB antibodies, and ROS production was determined by dihydroethidium staining in fresh frozen samples. RESULTS: The number of inflammatory aqueous cells and protein levels were lower in the groups treated with 10 and 1 mg/kg of echinochrome than in the untreated LPS group (p<0.01). Treatment with 10 and 1 mg/kg of echinochrome significantly reduced TNF-α concentrations in aqueous humor (p<0.01). The numbers of NFκB-positive cells and ROS signals were also reduced by echinochrome administration (p<0.05). CONCLUSIONS: Echinochrome ameliorated intraocular inflammation caused by EIU by reducing ROS production, thereby also decreasing the expression of NFκB and TNF-α. As a natural pigment, echinochrome may therefore be a promising candidate for the safe treatment of intraocular inflammation. The use of sea urchin shells and spines in health foods and medical products is thus both economically and environmentally meaningful.

Coupled Vis-NIR spectroscopy with chemometrics strategy for soil organic carbon prediction in the Agro-pastoral Transitional zone of northwest China.

Rapidly and accurately grasp the change of soil organic carbon content in farmland, which is of great significance in guiding the timely and effective mastery of farmland soil fertility and improvement of soil physical properties. In this study, an ASD FieldSpec 4 spectrometer was used to collect spectral reflectance data on 128 agricultural soil samples taken from Jingbian County, Yulin City, Shaanxi Province, China. Firstly, descriptive statistics of the SOC in the study area were performed, and secondly, after 10 spectral transformations were performed, the correlation analysis and the Boruta algorithm were used to extract the characteristic wavebands of soil organic carbon, respectively, in order to reduce the redundancy of the data. Finally, by comparing the accuracies of different strategies, we constructed a spectral prediction model of soil organic carbon in farmland of the Northwest Agricultural and Animal Husbandry Intertwined Zone that integrates the optimal preprocessing, feature selection strategy and modelling method. The results indicate that: 1) The mean SOC content of the farmland in the study area was low and at the nutrient deficient level, with the standard errors and coefficients of variation for the modelling and validation sets were 1.596 g kg-1, 1.457 g kg-1, 54 % and 52 %, respectively; 2) The shape and trend of spectral special curves with different SOC contents show consistency, and the SOC content is negatively correlated with spectral reflectance; 3) CA selects more feature bands, but the feature bands are more homogeneous, while the Boruta algorithm can effectively remove irrelevant variables and improve the SOC feature selection effect; 4) The SOC prediction model based on Boruta-FD-RF can be better for soil organic carbon estimation, with R2 of 0.899 and 0.748 for the training set and validation set, respectively, RMSE of 1.432 g kg-1 and 1.967 g kg-1, and RPD of 2.557 and 1.647, respectively. The results show that the SOC model established by integrating optimal spectral pre-processing, feature selection strategy and chemometrics strategy has obvious improvement in prediction accuracy and stability, and this study provides an important reference for the fast and accurate estimation of SOC content in farmland of Agro-pastoral Transitional zone in northwest China.

Postoperative abdominal herpes zoster complicated by intestinal obstruction: A case report.

BACKGROUND: Intestinal obstruction is a common occurrence in clinical practice. However, the occurrence of herpes zoster complicated by intestinal obstruction after abdominal surgery is exceedingly rare. In the diagnostic and treatment process, clinicians consider it crucial to identify the primary causes of its occurrence to ensure effective treatment and avoiding misdiagnosis. CASE SUMMARY: Herein, we present the case of a 40-year-old female patient with intestinal obstruction who underwent laparoscopic appendectomy and developed herpes zoster after surgery. Combining the patient's clinical manifestations and relevant laboratory tests, it was suggested that the varicella zoster virus reactivated during the latent period after abdominal surgery, causing herpes zoster. Subsequently, the herpes virus invaded the visceral nerve fibers, causing gastrointestinal dysfunction and loss of intestinal peristalsis, which eventually led to intestinal obstruction. The patient was successfully treated through conservative treatment and antiviral therapy and subsequently discharged from the hospital. CONCLUSION: Pseudo-intestinal obstruction secondary to herpes zoster infection is difficult to distinguish from mechanical intestinal obstruction owing to various causes. In cases of inexplicable intestinal obstructions, considering the possibility of a viral infection is essential to minimize misdiagnosis and missed diagnoses.

Association of vitamins B1 and B2 intake with early-onset sarcopenia in the general adult population of the US: a cross-sectional study of NHANES data from 2011 to 2018.

Background: Early-onset sarcopenia refers to the progressive loss of muscle mass and function that occurs at an early age. This condition perpetuates the vicious cycle of muscle loss and is associated with adverse outcomes. It is important to identify the contributing factors for early intervention and prevention. While diet is known to impact muscle mass, the association of B vitamins with early-onset sarcopenia remains unexplored. Objectives: To investigate the association of B vitamins intake with early-onset sarcopenia risk in a cross-sectional study. Methods: We conducted data analysis on a total of 8,711 participants aged between 20 and 59 years who took part in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Early-onset sarcopenia was defined as a SMI measured by DXA that was one standard deviation below the sex-specific mean of the reference population. B vitamins intake (B1, B2, B3, B6, B9, and B12) was assessed by 24-h dietary recall. We used weighted multiple logistic regression and RCS models to estimate the OR and 95% CI of sarcopenia by B vitamins intake, adjusting for demographic, physical, lifestyle, comorbidities, and nutritional covariates. Results: Higher intake of vitamin B1 was associated with a 22% lower sarcopenia risk (OR = 0.78, CI = 0.63-0.97, p = 0.022), and higher intake of vitamin B2 with a 16% lower risk (OR = 0.84, CI = 0.74-0.97, p = 0.012) in both genders. Gender-specific analyses showed a 28% reduction in sarcopenia risk among males with each additional mg of vitamin B1 intake (OR = 0.72, CI = 0.52-0.97, p = 0.038), and a 26% decrease among females with each additional mg of vitamin B2 intake (OR = 0.74, CI = 0.57-0.96, p = 0.021). No significant differences were found between vitamin B2 and males, or between vitamin B1 and females. The RCS model suggested a nonlinear relationship between vitamin B2 intake and sarcopenia risk (POverall = 0.001, PNonlinear = 0.033), with a plateau effect above 3 mg/d. Conclusion: Higher intake of vitamin B1 and B2 may lower the risk of early-onset sarcopenia, with gender differences. This suggests the potential of nutritional intervention by increasing these vitamins intake through diet and supplements. Further research is warranted to elucidate the mechanisms and design targeted interventions.

Exercise-induced Musclin determines the fate of fibro-adipogenic progenitors to control muscle homeostasis.

The effects of exercise on fibro-adipogenic progenitors (FAPs) are unclear, and the direct molecular link is still unknown. In this study, we reveal that exercise reduces the frequency of FAPs and attenuates collagen deposition and adipose formation in injured or disused muscles through Musclin. Mechanistically, Musclin inhibits FAP proliferation and promotes apoptosis in FAPs by upregulating FILIP1L. Chromatin immunoprecipitation (ChIP)-qPCR confirms that FoxO3a is the transcription factor of FILIP1L. In addition, the Musclin/FILIP1L pathway facilitates the phagocytosis of apoptotic FAPs by macrophages through downregulating the expression of CD47. Genetic ablation of FILIP1L in FAPs abolishes the effects of exercise or Musclin on FAPs and the benefits on the reduction of fibrosis and fatty infiltration. Overall, exercise forms a microenvironment of myokines in muscle and prevents the abnormal accumulation of FAPs in a Musclin/FILIP1L-dependent manner. The administration of exogenous Musclin exerts a therapeutic effect, demonstrating a potential therapeutic approach for muscle atrophy or acute muscle injury.

Characterization of the visually impaired patients with diabetes mellitus in Japan.

AIMS/INTRODUCTION: To conduct a multicenter survey of visually impaired patients with diabetes mellitus (DM) and to identify the physical and ocular characteristics that lead to blindness in Japan. MATERIALS AND METHODS: Visually impaired patients with diabetes mellitus in Japan were divided into blind and low-vision groups according to the World Health Organization classification. Data on parameters related to diabetes mellitus and ocular complications in the right and left eyes were collected from 19 highly advanced medical facilities and compared between the two groups. RESULTS: Among 408 visually impaired persons (blind group: 257, low-vision group: 151), 72.1% were under 70 years of age. The rates of neovascular glaucoma (NVG) (right eye, P = 0.041; left eye, P = 0.0031) or proliferative diabetic retinopathy (PDR) (right eye: P = 0.014, left eye: P = 0.0047) and the rate of proliferative membrane beyond half of the retinal area (right eye: P = 0.0263, left eye: P = 0.037) were significantly higher in the blind group. The direct cause of visual impairment was retinal atrophy, common in both groups. Neovascular glaucoma and diabetic macular edema were equally prevalent in the blind and low-vision groups, respectively. CONCLUSIONS: In Japan, blind patients with diabetes mellitus are characterized by severe conditions such as neovascular glaucoma and progressive proliferative diabetic retinopathy upon their initial visit to an advanced care facility. These results highlight the importance of monitoring retinopathy through regular ophthalmological examinations, internal medicine, and appropriate therapeutic intervention.

Expression of vascular endothelial growth factor C in human pterygium.

Vascular endothelial growth factor C (VEGF-C) and its receptor VEGFR-3 mediate lymphangiogenesis. In this study, we analyzed the expression of VEGF-C and VEGFR-3 as well as lymphatic vessels in the pterygium and normal conjunctiva of humans. Fifteen primary nasal pterygia and three normal bulbar conjunctivas, surgically removed, were examined in this study. The lymphatic vessel density (LVD) and blood vessel density were determined by the immunolabeling of D2-40 and CD31, markers for lymphatic and blood vessels, respectively. VEGF-C and VEGFR-3 expression in pterygial and conjunctival tissue proteins was detected by Western blotting and were evaluated using immunohistochemistry. The LVD was significantly higher in the pterygium than normal conjunctiva (p < 0.05). Western blot demonstrated high-level expression of VEGF-C and VEGFR-3 in the pterygium compared with normal conjunctiva. VEGF-C immunoreactivity was detected in the cytoplasm of pterygial and normal conjunctival epithelial cells. The number of VEGF-C-immunopositive cells in pterygial epithelial cells was significantly higher than in normal conjunctival cells (p < 0.05). VEGFR-3 immunoreactivity was localized in the D2-40-positive lymphatic endothelial cells. The present findings suggest the potential role of VEGF-C in the pathogenesis and development of a pterygium through lymphangiogenesis and the VEGF-C/VEGFR-3 pathway as a novel therapeutic target for the human pterygium.

Specific inhibition of serine/arginine-rich protein kinase attenuates choroidal neovascularization.

PURPOSE: To investigate the applicability of serine/arginine-rich protein kinase (SRPK)-specific inhibitor, SRPIN340, for attenuation of choroidal neovascularization (CNV) formation using a mouse model. METHODS: Laser photocoagulation was performed to induce CNV in C57BL/6J mice, followed by intravitreal injection of SRPIN340 or vehicle. Seven days after the treatment, the CNV size was evaluated using a flatmount technique. Protein levels of vascular endothelial growth factor (VEGF) and inflammation-associated molecules, such as monocyte chemoattractant protein (MCP)-1 and intercellular adhesion molecule (ICAM)-1, in the retinal pigment epithelium-choroid complex were measured with enzyme-linked immunosorbent assay. Expression levels of total Vegf, exon 8a-containing Vegf isoforms, and F4/80 (a specific marker for macrophage) were assessed using real-time PCR. RESULTS: SRPIN340 inhibited CNV formation in a dose-dependent manner. Compared with the vehicle, SRPIN340 significantly decreased the protein levels of VEGF, MCP-1, ICAM-1, and consequently inhibited macrophage infiltration. Furthermore, SRPIN340 suppressed the gene expression levels of total Vegf and exon 8a-containing Vegf isoforms. CONCLUSIONS: SRPIN340, a specific inhibitor of SRPK, suppressed Vegf expression and attenuated CNV formation. Our data suggest the possibility that SRPIN340 is applicable for neovascular age-related macular degeneration as a novel chemical therapeutics.

Expression of vascular endothelial growth factor and intravitreal anti-VEGF therapy with bevacizumab in vasoproliferative retinal tumors.

PURPOSE: To examine whether vasoproliferative retinal tumors (VPRTs) express vascular endothelial growth factor and respond to intravitreal bevacizumab injection. METHODS: Retrospective interventional case series. Intravitreal bevacizumab 1.25 mg was administered to 9 patients with VPRT-associated neovascularization or exudative retinal changes. The changes of the tumor size, best-corrected visual acuity, and central retinal thickness were evaluated before and after treatment. Immunohistochemistry with anti-vascular endothelial growth factor antibody in an excised tissue of VPRT during pars plana vitrectomy was performed. RESULTS: In two patients with small tumors (within two disk diameters), the tumors disappeared or regressed with only one injection of intravitreal bevacizumab injection. Larger tumors regressed after additional laser photocoagulation and/or cryotherapy without recurrence of exudative retinal changes in six eyes, although these did not regress by intravitreal bevacizumab injection alone. The mean logarithm of the minimal angle of resolution value of best-corrected visual acuity and central retinal thickness at the final visit were significantly improved compared with those of pretreatment (P = 0.02 and P = 0.03, respectively). Immunoreactivity for vascular endothelial growth factor was strongly detected in the resected tumor tissue. CONCLUSION: These results suggest that vascular endothelial growth factor derived from VPRTs causes retinal neovascularization or exudative retinal changes associated with VPRTs. Intravitreal bevacizumab may be a useful therapeutic option for these complications secondary to VPRTs.