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Biomedical subjects

Emily Y Chew

Publications and source records attributed to Emily Y Chew.

At least 19 recordsLinked to original sources
PubMed2025

Ophthalmic imaging as a measure of cardiovascular and neurological health: a multi-omic analysis of deep-learning derived phenotypes.

The eye is a recognised source of biomarkers for cardiovascular and neurodegenerative disease risk. Here, we characterise the breadth of these associations and identify biological axes that may mediate them. Using UK Biobank data, we developed a multi-omic analysis pipeline integrating physiological, radiomic, metabolomic, and genomic information. We trained adversarial autoencoders (Ret-AAE) to represent optical coherence tomography (OCT) images and colour fundus photographs as 256-dimensional embeddings. Ret-AAE derived embeddings were associated with a range of cardiovascular and neurodegenerative diseases, including ischaemic heart disease, cerebrovascular disease, Parkinson's disease, and dementia. Examining associations across diverse omics datasets, we provide evidence linking ophthalmic imaging features to neurological and cardiovascular anatomy and function, lipid metabolism, and gene sets associated with neurodegenerative pathology. Collectively, our findings demonstrate that ophthalmic features reflect complex, multisystem biological processes, and reinforce the role of the eye as a composite indicator of systemic health.

Journal Article↗
PubMed2007

Molecular pathology of eyes with von Hippel-Lindau (VHL) Disease: a review.

BACKGROUND: von Hippel-Lindau Disease (VHL) is an autosomal dominant inherited systemic cancer syndrome. Recently, many advances have contributed to the understanding of VHL pathophysiology. METHODS: In this article we review recent developments and summarize our findings in VHL molecular pathology related to retinal and optic nerve diseases. RESULTS: Loss of heterozygosity (LOH) within the VHL gene is detected in the stromal cells surrounding the capillary endothelial cells and admixed with glial cells in ocular hemangioblastomas. This finding is in line with similar findings in VHL-associated CNS hemangioblastoma and renal clear cell carcinomas. Increases of vascular endothelial growth factor (VEGF), hypoxia induced factor (HIF), and ubiquitin are found in ocular hemangioblastomas.Interestingly, tumorlet cells, which are composed of poorly differentiated small cells with prominent dark nuclei and little cytoplasm, as well as several stem cell markers, such as erythropoietin (Epo), Epo receptor (EpoR), and CD133, are present in ocular VHL lesions. CXCR4, a CXC chemokine receptor is also expressed in retinal VHL hemangioblastomas. CONCLUSIONS: These findings imply that VHL cells with LOH of the tumor suppressor gene, most likely originate from a hematopoietic/vascular lineage. Targeting these proteins and ischemic factors, not VEGF alone, may be a potential therapeutic approach for VHL-associated ocular hemangioblastomas.

Genes, Tumor Suppressor↗
PubMed2006

Synergic effect of polymorphisms in ERCC6 5' flanking region and complement factor H on age-related macular degeneration predisposition.

This study investigates age-related macular degeneration (AMD) genetic risk factors through identification of a functional single-nucleotide polymorphism (SNP) and its disease association. We chose ERCC6 because of its roles in the aging process, DNA repair, and ocular degeneration from the gene disruption. Bioinformatics indicated a putative binding-element alteration on the sequence containing C-6530>G SNP in the 5' flanking region of ERCC6 from Sp1 on the C allele to SP1, GATA-1, and OCT-1 on the G allele. Electrophoretic mobility shift assays displayed distinctive C and G allele-binding patterns to nuclear proteins. Luciferase expression was higher in the vector construct containing the G allele than that containing the C allele. A cohort of 460 advanced AMD cases and 269 age-matched controls was examined along with pathologically diagnosed 57 AMD and 18 age-matched non-AMD archived cases. ERCC6 C-6530>G was associated with AMD susceptibility, both independently and through interaction with an SNP (rs380390) in the complement factor H (CFH) intron reported to be highly associated with AMD. A disease odds ratio of 23 was conferred by homozygozity for risk alleles at both ERCC6 and CFH compared with homozygozity for nonrisk alleles. Enhanced ERCC6 expression was observed in lymphocytes from healthy donors bearing ERCC6 C-6530>G alleles. Intense immunostaining of ERCC6 was also found in AMD eyes from ERCC6 C-6530>G carriers. The strong AMD predisposition conferred by the ERCC6 and CFH SNPs may result from biological epistasis, because ERCC6 functions in universal transcription as a component of RNA pol I transcription complex.

5' Flanking Region↗
PubMed2006

An apolipoprotein E variant may protect against age-related macular degeneration through cytokine regulation.

Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness among the elderly in Western countries. Genetic factors, age, cigarette smoking, nutrition, and exposure to light have been identified as AMD risk factors. In this study, we investigated the association between ApoE C112R/R158C single nucleotide polymorphisms (which determine the E2, E3, and E4 isoforms) and age-related macular degeneration (AMD), and the mechanism underlying the association. Genomic DNA was extracted from 133 clinically screened controls, 94 volunteers with a younger mean age, 120 patients with advanced AMD, and 40 archived ocular AMD slides for single nucleotide polymorphism typing. The effects of recombinant ApoE isoforms on CCL2 (a chemokine), CX3CR1 (a chemokine receptor), and VEGF (a cytokine) expression in cultured human retinal pigment epithelium (RPE) cells were tested and serum cholesterol profiles of the clinically screened subjects were analyzed. ApoE112R (E4) distribution differed significantly between AMD patients and controls. ApoE112R allele frequency was 10.9% in the AMD group when compared with 16.5% in the younger controls and 18.8% in the clinically screened controls. The pathologically diagnosed archived AMD cases had the lowest allele frequency of 5%. No significant differences in ApoE158C (E2) distribution were observed among the groups. A meta-analysis of 8 cohorts including 4,289 subjects showed a strong association between AMD and 112R, but not 158C. In vitro studies found that recombinant ApoE suppresses CCL2 and VEGF expression in RPE cells. However, the E4 isoform showed more suppression than E3 in both cases. These results further confirm the association between ApoE112R and a decreased risk of AMD development. The underlying mechanisms may involve differential regulation of both CCL2 and VEGF by the ApoE isoforms.

Adult↗
PubMed2006

Screening options for diabetic retinopathy.

PURPOSE OF REVIEW: This review assesses the current status of the different methods used in screening for diabetic retinopathy. This update is particularly timely because the incidence of diabetes is rising rapidly and the number of patients with vision-threatening diabetic retinopathy is increasing. RECENT FINDINGS: We evaluate the different methods used and their results in improving the delivery of eye care to patients with diabetic retinopathy. In populations with poor access to ophthalmic care, screening techniques such as the nonmydriatic camera used in offices of primary care physicians may be useful in identifying lesions of diabetic retinopathy requiring treatment. One of the limitations is the lack of dilation and cataract formation, which may result in ungradable photographs. Patients with treatable lesions as well as those with ungradable photographs should be referred for comprehensive ocular examination. SUMMARY: Screening techniques do not replace the eye examination. Ophthalmologists can play an important role in diabetic care apart from treating eye disease. Counseling can be provided to patients regarding the importance of blood glucose and blood pressure control and may motivate patients to achieve strict glucose and blood pressure control.

Diabetic Retinopathy↗
PubMed2006

Dose-ranging study of lutein supplementation in persons aged 60 years or older.

PURPOSE: To examine the dose-response relationship between oral lutein supplementation and serum lutein concentrations in persons aged 60 years and older, with or without age-related macular degeneration (AMD). METHODS: Forty-five participants with no AMD, large drusen, or advanced AMD, were randomized to receive one of three doses (2.5, 5, or 10 mg) of lutein for 6 months and to be observed for 6 additional months after the cessation of lutein supplementation. RESULTS: The mean age of the participants (33 women) was 71 years (range: 60-91). The serum lutein concentrations of each dose group were similar before supplementation, increased at 1 month, and peaked by 3 months. Median serum concentrations of the 2.5-, 5-, and 10-mg groups from baseline to month 6 increased from 18.7 to 35.1 microg/dL (2-fold increase), from 17.8 to 59.2 microg/dL (2.9-fold increase), and from 15.1 to 66.8 microg/dL (4-fold increase), respectively (all P < 0.001). The increases in lutein serum concentrations did not vary with AMD disease severity (P = 0.98). No toxicity was observed with any dose of lutein. No significant changes were detected in visual acuity or visual field tests. CONCLUSIONS: Increasing doses of lutein supplements significantly increased the serum levels of lutein and zeaxanthin, and doses up to 10 mg were safely administered. A long-term large clinical trial is necessary to investigate the safety and efficacy of lutein in reducing the risk of the development of advanced AMD.

Administration, Oral↗
PubMed2006

The effect of lutein and zeaxanthin supplementation on metabolites of these carotenoids in the serum of persons aged 60 or older.

PURPOSE: To investigate the effect of lutein supplementation at doses of 2.5, 5.0, and 10 mg/d for 6 months on distribution of these carotenoids and their metabolites in the serum of elderly human subjects, with and without age-related macular degeneration. To determine whether supplementation with lutein can interact with the serum levels of other dietary carotenoids, retinol, and alpha-tocopherol. METHODS: Forty-five subjects received daily supplements of lutein (containing 5% zeaxanthin) for 6 months and were followed up for another 6 months after supplementation. Blood was collected at various intervals and lutein, zeaxanthin, and their metabolites in the sera were quantified by normal-phase high-performance liquid chromatography (HPLC)-UV/visible detection. Other dietary carotenoids, retinol, and alpha-tocopherol were identified and quantified on a C18 reversed phase HPLC column. RESULTS: After 6 months of supplementation with 10 mg of lutein, the increases in the mean serum levels from baseline were: 210 to 1000 nM/L (P < 0.0001) for lutein and 56 to 95 nM/L (P < 0.0001) for zeaxanthin. Similarly, the mean concentrations (nM/L) of carotenoid metabolites increased from 49 to 98 (P < 0.0001) for 3-hydroxy-beta,epsilon-caroten-3'-one (3'-oxolutein); 31 to 80 (P < 0.0001) for 3'-hydroxy-epsilon,epsilon-caroten-3-one; and 19 to 25 (P < 0.0001) for epsilon,epsilon-carotene-3,3'-dione. The serum levels of these carotenoids gradually decline within 6 months after supplementation. CONCLUSIONS: The increase in the serum levels of lutein/zeaxanthin correlates with increases in the serum levels of their metabolites that have previously been identified in the ocular tissues. Elderly human subjects with and without AMD can safely take supplements of lutein up to 10 mg/d for 6 months with no apparent toxicity or side effects.

Aged↗
PubMed2005

Expression of stem cells markers in ocular hemangioblastoma associated with von Hippel-Lindau (VHL) disease.

PURPOSE: To better understand the histogenesis of ocular hemangioblastomas associated with von Hippel-Lindau (VHL) disease. METHODS: We found that co-expression of Epo and EpoR may mediate developmental stagnation and induce proliferation of hemangioblastoma. All lesions were frozen and/or fixed in formalin and embedded in paraffin. The specimens were sectioned and subjected to routine histology, immunohistochemistry and molecular analyses. Avidin-biotin-complex immunoperoxidase was used to evaluate the expression of erythropoietin (Epo), Epo receptor (EpoR), CD31, CD34, CD117, and CD133. Ocular hemangioblastoma cells were microdissected in order to determine expression of Epo and EpoR transcripts using reverse transcription-polymerase chain reaction. RESULTS: Tumorlet-like cells were identified in retinal and optic nerve hemangioblastomas. Co-expression of Epo and EpoR at both protein and messenger levels was detected in many hemangioblastoma cells. In addition, ocular VHL lesions expressed several stem cell markers including CD133 to various degrees. CONCLUSIONS: The data suggest that VHL disease-associated ocular hemangioblastomas are comprised of developmentally arrested stem cells including hemangioblasts, endothelial, and neuronal progenitor cells. We found that co-expression of Epo and EpoR may not only mediate developmental stagnation, but may also induce proliferation. Suppression of the growth of AC133/CD133 positive stem cells might be considered as one of the therapeutic targets for VHL-associated hemangioblastoma.

Antigens, CD↗
PubMed2005

Complement factor H polymorphism in age-related macular degeneration.

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. We report a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. Among 116,204 single-nucleotide polymorphisms genotyped, an intronic and common variant in the complement factor H gene (CFH) is strongly associated with AMD (nominal P value <10(-7)). In individuals homozygous for the risk allele, the likelihood of AMD is increased by a factor of 7.4 (95% confidence interval 2.9 to 19). Resequencing revealed a polymorphism in linkage disequilibrium with the risk allele representing a tyrosine-histidine change at amino acid 402. This polymorphism is in a region of CFH that binds heparin and C-reactive protein. The CFH gene is located on chromosome 1 in a region repeatedly linked to AMD in family-based studies.

Aged↗
PubMed2005

A simplified severity scale for age-related macular degeneration: AREDS Report No. 18.

OBJECTIVE: To develop a simplified clinical scale defining risk categories for development of advanced age-related macular degeneration (AMD). METHODS: Following development of a detailed scale for individual eyes based on gradings of fundus photographs in the Age-Related Eye Disease Study, rates of progression to advanced AMD were assessed in cross-tabulations of presence or absence in each eye of 2 easily identified retinal abnormalities, drusen and pigment abnormalities. Large drusen and any pigment changes were particularly predictive of developing advanced AMD. RESULTS: The scoring system developed for patients assigns to each eye 1 risk factor for the presence of 1 or more large (> or = 125 microm, width of a large vein at disc margin) drusen and 1 risk factor for the presence of any pigment abnormality. Risk factors are summed across both eyes, yielding a 5-step scale (0-4) on which the approximate 5-year risk of developing advanced AMD in at least one eye increases in this easily remembered sequence: 0 factors, 0.5%; 1 factor, 3%; 2 factors, 12%; 3 factors, 25%; and 4 factors, 50%. For persons with no large drusen, presence of intermediate drusen in both eyes is counted as 1 risk factor. CONCLUSION: This simplified scale provides convenient risk categories for development of advanced AMD that can be determined by clinical examination or by less demanding photographic procedures than used in the Age-Related Eye Disease Study.

Disease Progression↗
PubMed2005

Central visual function and the NEI-VFQ-25 near and distance activities subscale scores in people with type 1 and 2 diabetes.

PURPOSE: To investigate relationships between clinical measures of central visual function and NEI-VFQ-25 Near and Distance Activities subscales in patients with diabetic retinopathy. DESIGN: Clinic-based, cross-sectional, observational study. METHODS: The NEI-VFQ-25 was administered to 170 people with type 1 or 2 diabetes before an ocular examination that included visual acuity, contrast sensitivity, and central visual fields. Multiple linear regression and exact multiple logistic regression were used to assess the relationship between poor acuity (<69 letters), poor contrast sensitivity (<1.5 log units), and abnormal visual fields (mean deviation < or = -5dB) and NEI-VFQ-25 subscale scores. RESULTS: Final multivariable linear models explained a beta = 4.7 letter difference (P < or = .001) for each 25-point Near Activities subscale score difference. Similar effects were observed for the Distance Activities subscale, although the magnitudes of regression and partial correlation coefficients were lower (beta = 3.3 letters, P < or = .01). Final logistic regression models on abnormal clinical categories of central visual function demonstrated relationships only with the Near Activities subscale. For a 1-point change in Near Activities subscale score, the odds of obtaining a poor score for visual acuity, central visual fields, and contrast sensitivity changed by 0.08 (P < or = .001), 0.07 (P < or = .05), and 0.12 (P < or = .001), respectively. CONCLUSIONS: NEI-VFQ-25 Near and Distance Activities subscales demonstrate utility as measures of central visual function in persons with type 1 or 2 diabetes. Low scores on the NEI-VFQ-25 may reflect poor central visual fields and contrast sensitivity in addition to poor visual acuity.

Adult↗
PubMed2005

The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina.

In this work we advance the hypothesis that omega-3 (omega-3) long-chain polyunsaturated fatty acids (LCPUFAs) exhibit cytoprotective and cytotherapeutic actions contributing to a number of anti-angiogenic and neuroprotective mechanisms within the retina. omega-3 LCPUFAs may modulate metabolic processes and attenuate effects of environmental exposures that activate molecules implicated in pathogenesis of vasoproliferative and neurodegenerative retinal diseases. These processes and exposures include ischemia, chronic light exposure, oxidative stress, inflammation, cellular signaling mechanisms, and aging. A number of bioactive molecules within the retina affect, and are effected by such conditions. These molecules operate within complex systems and include compounds classified as eicosanoids, angiogenic factors, matrix metalloproteinases, reactive oxygen species, cyclic nucleotides, neurotransmitters and neuromodulators, pro-inflammatory and immunoregulatory cytokines, and inflammatory phospholipids. We discuss the relationship of LCPUFAs with these bioactivators and bioactive compounds in the context of three blinding retinal diseases of public health significance that exhibit both vascular and neural pathology. How is omega-3 LCPUFA status related to retinal structure and function? Docosahexaenoic acid (DHA), a major dietary omega-3 LCPUFA, is also a major structural lipid of retinal photoreceptor outer segment membranes. Biophysical and biochemical properties of DHA may affect photoreceptor membrane function by altering permeability, fluidity, thickness, and lipid phase properties. Tissue DHA status affects retinal cell signaling mechanisms involved in phototransduction. DHA may operate in signaling cascades to enhance activation of membrane-bound retinal proteins and may also be involved in rhodopsin regeneration. Tissue DHA insufficiency is associated with alterations in retinal function. Visual processing deficits have been ameliorated with DHA supplementation in some cases. What evidence exists to suggest that LCPUFAs modulate factors and processes implicated in diseases of the vascular and neural retina? Tissue status of LCPUFAs is modifiable by and dependent upon dietary intake. Certain LCPUFAs are selectively accreted and efficiently conserved within the neural retina. On the most basic level, omega-3 LCPUFAs influence retinal cell gene expression, cellular differentiation, and cellular survival. DHA activates a number of nuclear hormone receptors that operate as transcription factors for molecules that modulate reduction-oxidation-sensitive and proinflammatory genes; these include the peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and the retinoid X receptor. In the case of PPAR-alpha, this action is thought to prevent endothelial cell dysfunction and vascular remodeling through inhibition of: vascular smooth muscle cell proliferation, inducible nitric oxide synthase production, interleukin-1 induced cyclooxygenase (COX)-2 production, and thrombin-induced endothelin 1 production. Research on model systems demonstrates that omega-3 LCPUFAs also have the capacity to affect production and activation of angiogenic growth factors, arachidonic acid (AA)-based vasoregulatory eicosanoids, and MMPs. Eicosapentaenoic acid (EPA), a substrate for DHA, is the parent fatty acid for a family of eicosanoids that have the potential to affect AA-derived eicosanoids implicated in abnormal retinal neovascularization, vascular permeability, and inflammation. EPA depresses vascular endothelial growth factor (VEGF)-specific tyrosine kinase receptor activation and expression. VEGF plays an essential role in induction of: endothelial cell migration and proliferation, microvascular permeability, endothelial cell release of metalloproteinases and interstitial collagenases, and endothelial cell tube formation. The mechanism of VEGF receptor down-regulation is believed to occur at the tyrosine kinase nuclear factor-kappa B (NFkappaB). NFkappaB is a nuclear transcription factor that up-regulates COX-2 expression, intracellular adhesion molecule, thrombin, and nitric oxide synthase. All four factors are associated with vascular instability. COX-2 drives conversion of AA to a number angiogenic and proinflammatory eicosanoids. Our general conclusion is that there is consistent evidence to suggest that omega-3 LCPUFAs may act in a protective role against ischemia-, light-, oxygen-, inflammatory-, and age-associated pathology of the vascular and neural retina.

Adolescent↗
PubMed2005

Serum inflammatory markers in diabetic retinopathy.

PURPOSE: To evaluate the association of serum factors with the severity of diabetic retinopathy and to assess their presence in retinal tissue obtained at autopsy. METHODS: The following serum factors of 93 subjects were examined at the National Eye Institute (NEI) clinical center: the chemokines regulated on activation, normal T-cell expressed and presumably secreted (RANTES)/CCL5, epithelial neutrophil activator (ENA)-78/CXCL5, interferon-induced protein (IP)-10/CXCL10, stromal cell-derived factor (SDF)-1alpha/CXCLl2, monocyte chemoattractant protein (MCP)-1/CCL2, macrophage inflammatory protein (MIP)-1alpha/CCL3, interleukin (IL)-8/CXCL8; the cytokine IL-6; the cell adhesion molecules intercellular adhesion molecule (ICAM-1/CD54) and vascular cell adhesion molecule (VCAM/CD106); and the growth factor vascular endothelial growth factor (VEGF). Logistic regression was performed to assess the association of these factors with age, sex, severity of retinopathy, hemoglobin A(1C), total cholesterol, creatinine, duration of diabetes, and presence of macular edema. The outcome assessed was severity of retinopathy. Frozen sections of two donor eyes obtained at autopsy from a donor with documented severe nonproliferative diabetic retinopathy and diabetic macular edema and of a normal nondiabetic eye were processed by immunoperoxidase staining with primary antibodies against RANTES, MCP-1, ICAM-1, and LFA-1alpha/CD11a. RESULTS: The levels of RANTES and SDF-1alpha were significantly elevated in patients with at least severe nonproliferative diabetic retinopathy compared with those with less severe diabetic retinopathy (P < 0.001 and 0.007, respectively). Positive immunostaining was observed in the inner retina for MCP-1 and RANTES of the patient with diabetes. Staining was strongly positive throughout the diabetic retina for ICAM-1. Normal retinal tissues showed little reactivity. CONCLUSIONS: Serum chemokines were significantly elevated in patients with at least severe nonproliferative diabetic retinopathy compared with those who had less severe retinopathy. Elevated levels of the chemokines and cell adhesion molecules were also identified in eyes of a donor with ischemic diabetic retinopathy. These findings provide evidence to support the role of inflammation in the pathogenesis of diabetic retinopathy.

Biomarkers↗
PubMed2005

Associations of mortality and diabetes complications in patients with type 1 and type 2 diabetes: early treatment diabetic retinopathy study report no. 27.

OBJECTIVE: Diabetes is a leading cause of morbidity and mortality. The purpose of this study is to assess the associations between diabetes complications and mortality in the Early Treatment Diabetic Retinopathy Study (ETDRS). RESEARCH DESIGN AND METHODS: We examined demographic, clinical, and laboratory characteristics of the 3,711 subjects enrolled in the ETDRS, a randomized controlled clinical trial designed to evaluate the role of laser photocoagulation and aspirin therapy for diabetic retinopathy. The outcome assessed was all-cause mortality. Multivariable Cox proportional hazards regression was used to assess associations between diabetes complications and mortality for type 1 and type 2 diabetes separately. RESULTS: The 5-year estimates of all-cause mortality were 5.5 and 18.9% for patients with type 1 and type 2 diabetes, respectively. In patients with type 1 diabetes, amputation (hazard ratio [HR] 5.08 [95% CI 2.06-12.54]) and poor visual acuity (1.74 [1.10-2.75]) remained significantly associated with mortality, after adjusting for other diabetes complications and baseline characteristics. In patients with type 2 diabetes, macrovascular disease and worsening levels of nephropathy, neuropathy, retinopathy, and visual acuity are associated with progressively increasing risks of mortality, after controlling for other baseline risk factors. CONCLUSIONS: Amputation is the strongest predictor for mortality in patients with type 1 diabetes. All complications independently predict mortality in patients with type 2 diabetes. There is an increased risk for mortality as the degree of each complication worsens. Additional studies are needed to investigate the effectiveness of tertiary prevention to decrease mortality in these patients.

Adult↗
PubMed2005

Analysis of Hemicentin-1, hOgg1, and E-selectin single nucleotide polymorphisms in age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) is a common disease in which both environmental and genetic factors have been implicated. Various single nucleotide polymorphisms (SNPs) have been correlated, through candidate gene association studies, with age-related diseases, including AMD. Recently we identified an association between AMD and two SNPs in CX3CR1, which encodes a chemokine receptor. This study investigates the Hemicentin-1 (an extracellular matrix protein) Q5345R, hOgg1 (DNA repair gene) S326C, and E-selectin (an adhesion molecule) S149R SNPs in association with AMD. METHODS: Genomic DNA was extracted from peripheral blood of 89 patients with advanced AMD, 97 age-matched controls without clinical AMD, and 170 random unscreened healthy volunteers. DNA was subjected to polymerase chain reaction amplification coupled with the restriction fragment length polymorphism assay. RESULTS: The distribution of the Hemicentin-1 Q5345R, hOgg1 S326C, and E-selectin S149R SNPs did not differ significantly (all P values > .05) between the AMD patients and controls. Hemincentin-1 5345R was not found in any subject. hOgg1 326C allele frequency was 21.35% (38 of 178) in the AMD group compared with 19.12% (65 of 340) in the random controls and 19.59% (38 of 194) in the age-matched controls. E-selectin 149R allele frequencies were 8.99% (16 of 178) in AMD cases, 9.41% (32 of 340) in random controls, and 10.82% (21 of 194) in age-matched controls. CONCLUSIONS: We were not able to demonstrate an association between the Hemicentin-1, hOgg1, and E-selectin SNPs and AMD development in the currently available cases and controls. Further candidate genes, particularly those involved in extracellular matrix, oxidative stress, and immune system functions, are currently being screened in our laboratory.

Adult↗
PubMed2004

The involvement of sequence variation and expression of CX3CR1 in the pathogenesis of age-related macular degeneration.

This study examined the association between the sequence variation/expression of CX3CR1, a chemokine receptor, and age-related macular degeneration (AMD). Peripheral blood from 85 AMD patients and 105 subjects without AMD (controls), as well as ocular tissue from 40 pathological sections with AMD and two normal eye sections, were screened for V249I and T280M, two single nucleotide polymorphisms (SNPs) in CX3CR1. An increased prevalence, with the highest odds ratio of 3.57, of the I249 and M280 carriers was found among the AMD cases as compared with the controls. When comparing CX3CR1 expression in the archived eye sections, CX3CR1 transcripts were not detectable in the maculae of AMD eyes bearing T/M280; however, transcripts were detected in the maculae of normal eyes bearing T/T280 or T/M280 as well as in the AMD maculae bearing T/T280. Furthermore, lower CX3CR1 protein expression was observed in the maculae of AMD eyes bearing T/M280 compared with the controls bearing T/T280. The I249 and M280 alleles result in a lowered number of receptor binding sites and a decreased ligand affinity. Our data suggest that a decrease, caused by sequence variation and/or lower CX3CR1 expression, in CX3CR1-induced cellular activities could contribute to AMD development.

Aged↗
PubMed2004

Risk factors for renal replacement therapy in the Early Treatment Diabetic Retinopathy Study (ETDRS), Early Treatment Diabetic Retinopathy Study Report No. 26.

BACKGROUND: Diabetes is a leading cause of end-stage renal disease (ESRD). The purpose of this study is to assess the risk factors for renal replacement therapy (RRT) in the Early Treatment Diabetic Retinopathy Study (ETDRS). METHODS: We examined demographic, clinical, and laboratory characteristics of the 2226 subjects with complete laboratory data enrolled in the ETDRS. The primary renal variable evaluated was the time to development of renal replacement therapy, defined as the need for dialysis or transplantation. Multivariable Cox proportional hazards regression was used to assess risk factors for type 1 and type 2 diabetes separately. RESULTS: The 5-year estimated incidence of RRT in the entire ETDRS population was 10.2% and 9.8% for patients with type 1 and type 2 diabetes, respectively. Of those patients with complete data, 127 of 934 (14%) of patients with type 1 diabetes, and 150 of 1292 (12%) patients with type 2 diabetes required RRT during the study. Baseline risk factors common to type 1 and type 2 diabetes included elevated total cholesterol, and serum creatinine; and low serum albumin and anemia. Other risk factors significant in type 1 diabetes included body mass index (BMI), shorter duration of diabetes, elevated hemoglobin A(1c) (HbA(1c)), elevated systolic blood pressure, and the development of proliferative diabetic retinopathy. Risk factors significant in type 2 diabetes, but not type 1 diabetes, included younger age, proteinuria, and elevated triglycerides. CONCLUSION: In this study, major modifiable risk factors such as hypertension, dyslipidemia, and hyperglycemia were found to be predictive of RRT. Other predictors were markers of vascular pathology and inflammation, proteinuria, hypoalbuminemia, and increased serum creatinine. Controlled clinical trials with treatment strategies that improve serum lipid levels, systemic blood pressure, glycemic control, and markers of inflammation may be important in furthering our knowledge on the pathogenesis of diabetic complications such as nephropathy and ESRD.

Adult↗