Background Retinal ischemia induces intraocular neovascularization, which often leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by stimulating the release of angiogenic molecules. Vascular endothelial growth factor (VEGF) is an endothelial-cell-specific angiogenic factor whose production is increased by hypoxia. Methods We measured the concentration of VEGF in 210 specimens of ocular fluid obtained from 164 patients undergoing intraocular surgery, using both radioimmunoassays and radioreceptor assays. Vitreous proliferative potential was measured with in vitro assays of the growth of retinal endothelial cells and with VEGF-neutralizing antibody. Results VEGF was detected in 69 of 136 ocular-fluid samples from patients with diabetic retinopathy, 29 of 38 samples from patients with neovascularization of the iris, and 3 of 4 samples from patients with ischemic occlusion of the central retinal vein, as compared with 2 of 31 samples from patients with no neovascular disorders (P<0.00...

Vascular Endothelial Growth Factor In Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal Disorders

Age-related macular degeneration (AMD) is the leading cause of severe central visual impairment among the elderly and is associated both with environmental factors such as smoking and with genetic factors. Here, 167 unrelated AMD patients were screened for alterations in ABCR, a gene that encodes a retinal rod photoreceptor protein and is defective in Stargardt disease, a common hereditary form of macular dystrophy. Thirteen different AMD-associated alterations, both deletions and amino acid substitutions, were found in one allele of ABCR in 26 patients (16%). Identification of ABCR alterations will permit presymptomatic testing of high-risk individuals and may lead to earlier diagnosis of AMD and to new strategies for prevention and therapy.

Mutation of the Stargardt Disease Gene (ABCR) in Age-related Macular Degeneration

We consider the problem of assessing associations between multiple related outcome variables, and a single explanatory variable of interest. This problem arises in many settings, including genetic association studies, where the explanatory variable is genotype at a genetic variant. We outline a framework for conducting this type of analysis, based on Bayesian model comparison and model averaging for multivariate regressions. This framework unifies several common approaches to this problem, and includes both standard univariate and standard multivariate association tests as special cases. The framework also unifies the problems of testing for associations and explaining associations – that is, identifying which outcome variables are associated with genotype. This provides an alternative to the usual, but conceptually unsatisfying, approach of resorting to univariate tests when explaining and interpreting significant multivariate findings. The method is computationally tractable genome-wide for modest numbers of phenotypes (e.g. 5–10), and can be applied to summary data, without access to raw genotype and phenotype data. We illustrate the methods on both simulated examples, and to a genome-wide association study of blood lipid traits where we identify 18 potential novel genetic associations that were not identified by univariate analyses of the same data.

/pdf/a-unified-framework-for-association-analysis-with-multiple-1jl0m7fbrh.pdf

A Unified Framework for Association Analysis with Multiple Related Phenotypes

Complement factor H (FH) is an important regulator of the alternative complement pathway. The Y402H polymorphism within the seventh short consensus repeat of FH was recently shown to be associated with age-related macular degeneration, the most common cause of irreversible blindness in the Western world. We examined the effects of this polymorphism on various FH functions. FH purified from sera of age-related macular degeneration patients homozygous for the FH402H variant showed a significantly reduced binding to C-reactive protein (CRP), an acute phase protein, as compared with FH derived from unaffected controls homozygous for the FH402Y variant. Strongly reduced binding to CRP was also observed with a recombinant fragment of FH (short consensus repeat 5–7) containing the same amino acid change. Because the interaction of CRP and FH promotes complement-mediated clearance of cellular debris in a noninflammatory fashion, we propose that the reduced binding of FH402H to CRP could lead to an impaired targeting of FH to cellular debris and a reduction in debris clearance and enhanced inflammation along the macular retinal pigmented epithelium-choroid interface in individuals with age-related macular degeneration.

Y402H Polymorphism of Complement Factor H Affects Binding Affinity to C-Reactive Protein

Importance In the past decade, significant progress in genomic medicine and technologic developments has revolutionized our approach to common complex disorders in many areas of medicine, including ophthalmology. A disorder that still needs major genetic progress is diabetic retinopathy (DR), one of the leading causes of blindness in adults. Objective To perform a literature review, present the current findings, and highlight some key challenges in DR genetics. Design, Setting, and Participants We performed a thorough literature review of the genetic factors for DR, including heritability scores, twin studies, family studies, candidate gene studies, linkage studies, and genome-wide association studies (GWASs). Main Outcome Measures Environmental and genetic factors for DR. Results Although there is clear demonstration of a genetic contribution in the development and progression of DR, the identification of susceptibility loci through candidate gene approaches, linkage studies, and GWASs is still in its infancy. The greatest obstacles remain a lack of power because of small sample size of available studies and a lack of phenotype standardization. Conclusions and Relevance The field of DR genetics is still in its infancy and is a challenge because of the complexity of the disease. This review outlines some strategies and lessons for future investigation to improve our understanding of this complex genetic disorder.

https://jamanetwork.com/journals/jamaophthalmology/articlepdf/1763095/eoi130159.pdf

Challenges in elucidating the genetics of diabetic retinopathy.

Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) gene are associated with diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM). Methods: A total of 268 patients with T2DM (129 with DR and 139 without DR) were recruited and enrolled in the study. Patients with T2DM were assigned to a DR group or a diabetic-without-retinopathy group, based on the duration of diabetes and grading of fundus images. Genotypes of eight SNPs in the VEGF gene (rs699947, rs833061, rs13207351, rs2010963, rs833069, rs2146323, rs3025021, and rs3025039) were analyzed using a mass-array genotyping system, and an association study was performed. Results: After adjusting for covariates, a significant association of DR was observed with the homozygous genotype of the minor allele for promoter SNPs rs699947 (odds ratio (OR)=3.54, 95% confidence interval (CI): 1.12–11.19), rs833061 (OR=3.72, 95% CI: 1.17–11.85) and rs13207351 (OR=3.76, 95% CI: 1.21–11.71). A significant association of DR was also observed with haplotype ACA, as defined by minor alleles of promoter SNPs rs699947, rs833061, and rs13207351 (OR=1.52, 95% CI: 1.03–2.24), and haplotype GAA, as defined by SNPs rs2010963, rs833069, and rs2146323 (OR=1.62, 95% CI: 1.08–2.41). Conclusions: Our data suggest that polymorphisms in the promoter region of the VEGF gene increase the risk of DR in Chinese patients with T2DM.

/pdf/polymorphisms-in-the-vascular-endothelial-growth-factor-gene-3ld93bprjg.pdf

Polymorphisms in the vascular endothelial growth factor gene and the risk of diabetic retinopathy in Chinese patients with type 2 diabetes.

Chronic obstructive pulmonary disease (COPD) is a common pulmonary disease characterized by persistent respiratory symptoms and airflow obstruction. In addition to lung diseases, chronic obstructive pulmonary disease (COPD) is often associated with other organ diseases, and sarcopenia is one of the common diseases. In recent years, multiple factors have been proposed to influence muscle dysfunction in COPD patients, including systemic and local inflammation, oxidative stress, hypoxia, hypercapnia, protein synthesis, catabolic imbalance, nutritional changes, disuse, ageing, and the use of medications such as steroids. These factors alone or in combination can lead to a reduction in muscle mass and cross-sectional area, deterioration of muscle bioenergy metabolism, defects in muscle repair and regeneration mechanisms, apoptosis and other anatomical and/or functional pathological changes, resulting in a decrease in the muscle’s ability to work. This article reviews the research progress of possible pathogenesis of sarcopenia in COPD.

/pdf/pathogenesis-of-sarcopenia-in-chronic-obstructive-pulmonary-1ldvjpty.pdf

Pathogenesis of sarcopenia in chronic obstructive pulmonary disease

OBJECTIVE To investigate the association of diabetic self-management with the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus. METHODS Cross-sectional study. Recruited patients with type 2 diabetes mellitus in the Desheng community of urban Beijing between November 2009 and May 2011. All patients were surveyed using a standardized questionnaire and underwent detailed ophthalmic examination. Patients were classified into DR group or diabetic without retinopathy (DWR) group according to the grading of fundus color photographs using the Early Treatment of Diabetic Retinopathy Study (ETDRS) standard grading protocol. In the DR group, proliferative diabetic retinopathy (PDR) was further defined. The overall levels of diabetes self-management in the study population were assessed and compared for the differences between DR and DWR, PDR and NPDR groups. RESULTS One thousand one hundred patients with type 2 diabetes mellitus were recruited. The prevalence of DR was 32.1% (353/1100) in the study population. Sixty-three percent (652/1035) of patients had glycated hemoglobin (HbA1c) level less than 7.0%. The majority of patients (85.4%, 916/1072) conducted a diet control, 77.3% (827/1070) exercised, 56.0% (609/1088) monitored blood glucose regularly, 56.8% (416/733) detected HbA1c more than once every six months, 71.7% (762/1062) had ophthalmologic examination after the diagnosis of diabetes mellitus, and 47.9% (525/1097) had mydriatic check-up. Increased risk of DR was associated with longer duration of diabetes (more than 10 years) (OR = 3.90, 95% CI:2.97-5.51, P < 0.05), higher HbA1c level of ≥ 7.0% (OR = 3.23, 95% CI:2.44-4.28, P < 0.05), insulin therapy (OR = 4.82, 95% CI:3.55-6.57, P < 0.05), male gender (OR = 1.41, 95% CI:1.08-1.84, P < 0.05), lower level of education (OR = 1.90, 95% CI:1.39-2.62, P < 0.05), lower monthly income (OR = 1.46, 95% CI:1.12-1.91, P < 0.05), lower obedience to diet control (OR = 1.72, 95% CI:1.22-2.43, P < 0.05), no exercise (OR = 1.42, 95% CI:1.04-1.94, P < 0.05), change of therapeutic protocol during the last five years (OR = 1.78, 95% CI:1.32-2.41, P < 0.05), and family history of diabetes (OR = 1.35, 95% CI:1.01-1.78, P < 0.05). Increased risk of PDR was associated with the diagnosis age of diabetes (OR = 0.92, 95% CI:0.89-0.95, P < 0.05), longer duration of diabetes (more than 10 years) (OR = 4.54, 95% CI:1.95-12.32, P < 0.05), and insulin therapy (OR = 4.85, 95% CI:2.34-10.90, P < 0.05). In the multifactor logistic regression model, male gender (OR = 2.21, 95% CI:1.57-3.11, P < 0.05), lower level of education (OR = 1.98, 95% CI:1.33-2.94, P < 0.05), lower monthly income (OR = 1.66, 95% CI:1.15-2.39, P < 0.05) ,longer duration of diabetes (more than 10 years) (OR = 2.46, 95% CI:1.77-3.41, P < 0.05) ,HbA1c ≥ 7.0% (OR = 2.24, 95% CI:1.64-3.07, P < 0.05) and insulin therapy (OR = 3.38, 95% CI:2.38-4.8, P < 0.05) were associated with higher risk of DR. The diagnosis age of diabetes (OR = 0.94, 95% CI:0.91-0.98, P < 0.05) and insulin therapy (OR = 3.49, 95% CI:1.47-8.27, P < 0.05) were associated with PDR. CONCLUSION Higher risk of DR is associated with longer duration of diabetes,insulin therapy, higher HbA1c level, male gender, and lower level of education, whereas higher risk of DR is also associated with lower obedience to diet control and less exercise, which suggest that lower level of diabetic self-management increased the risk of DR.

[Diabetes self-management and its association with diabetic retinopathy in patients with type 2 diabetes].

The purpose of this study was to investigate the role of HtrA serine peptidase 1 (HTRA1) in the proliferation and migration of cells of the human retinal pigment epithelial cell line ARPE-19, and the possible mechanisms involved. ARPE-19 cells were transduced by a recombinant lentiviral vector carrying HTRA1-shRNA to knockdown HTRA1 expression. Subsequent HTRA1 gene and HTRA1 protein levels in these cells and control cells were detected by quantitative real-time PCR and Western blot, respectively. Changes in cell proliferation and migration associated with the inhibition of HTRA1 expression were assessed, as well as changes in the mRNA levels of transforming growth factor beta 1 (TGFB1), bone morphogenetic protein 4 (BMP4), and bone morphogenetic protein 2 (BMP2). The recombinant lentivirus carrying HTRA1-shRNA was successfully generated, as evidenced by reduced levels of HTRA1 mRNA and HTRA1 protein in ARPE-19 cells. The knockdown of HTRA1 in ARPE-19 cells was associated with reduced cellular proliferation and migration, and increased mRNA levels of TGF-β1, BMP4, and BMP2. Silence of the HTRA1 gene was associated with significantly higher levels of TGF-β1, BMP4, and BMP2 mRNA and reduction in the proliferation and migration of ARPE-19 cells.

Inhibition of cell proliferation and migration after HTRA1 knockdown in retinal pigment epithelial cells

Purpose: We identified a large Chinese family with X-linked juvenile retinoschisis. The purpose of this study was to report the clinical findings of the family and to identify the genetic mutation by screening the retinoschisis 1 (RS1) gene. Methods: Family history was collected and all family members underwent routine ophthalmic examination. Venous blood was collected from family members and genomic DNA was extracted. The exons of RS1 were screened by PCR followed by direct sequencing and/or restriction enzyme digestion. Results: The pedigree of interest was a four-generation family with 52 family members, including seven affected individuals. The proband was a 5-year-old boy showing highly elevated bullous retinoschisis with moderate vitreous hemorrhage in both eyes. Vitrectomy was performed in the left eye of the proband. Five affected males showed large peripheral retinoschisis in both eyes, either involving the macula or combined with foveal stellate cystic change. One of the affected family members showed only a foveal stellate cystic change in both eyes without periphery retinoschisis. Visual acuity of affected individuals ranged from hand motion to 0.4. The R213W mutation in exon 6 of RS1 was identified in all affected individuals, predicting an amino acid substitution of arginine to tryptophan at codon 213. Conclusions: Our data show that the R213W mutation in RS1 causes various severities of retinoschisis in a large Chinese family, providing further evidence for X-linked juvenile retinoschisis phenotypic variability. X-linked juvenile retinoschisis (XLRS) is a hereditary retinal disease characterized by a splitting of the neurosensory retina [1]. It is a major cause of juvenile retinal degeneration in males [2], with an estimated prevalence of 1 in 15,000 to 1 in 30,000 [3]. The typical clinical manifestations of XLRS include foveal stellate cystic changes and peripheral retinoschisis. Symptoms, including visual impairment, squint, or nystagmus, usually appear at age 4 to 8 years, and visual deterioration often progresses during the first to second decades of life [4]. Thereafter the disease is mainly stationary or slowly progressive. By the age of 40 to 50 years, macular degeneration often occurs, causing additional visual failure [5]. In addition, severe vision loss can come from secondary complications, such as vitreous hemorrhage, retinal detachment, and neovascular glaucoma. Female carriers of the disease are unaffected. XLRS is caused by mutations in the retinoschisis 1 (RS1) gene localized at chromosome Xp22.2 [6]. The RS1 gene has six exons and encodes a 224 amino acid protein called retinoschisin, which is primarily expressed in retina and reveals an important role in retinal cell adhesion [7]. More than 100 disease-causing mutations in RS1 have been reported, including missense/nonsense mutations, deletions,

/pdf/r213w-mutation-in-the-retinoschisis-1-gene-causes-x-linked-pyz2jmxvjm.pdf

R213W mutation in the retinoschisis 1 gene causes X-linked juvenile retinoschisis in a large Chinese family.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Kai Ma

Author Tools

Chat about Author