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The metabolic syndrome and severity of diabetic retinopathy.
Clin Ophthalmol. 2015;9:757-64
Authors: Chen JJ, Wendel LJ, Birkholz ES, Vallone JG, Coleman AL, Yu F, Mahajan VB
BACKGROUND: While metabolic syndrome has been strongly implicated as a risk factor for macrovascular diseases, such as stroke and cardiovascular disease, its relationship with microvascular diseases, including diabetic retinopathy, has been less defined. The purpose of this pilot study was to investigate the association between metabolic syndrome and the presence and severity of diabetic retinopathy.
METHODS: A retrospective case-control chart review at the University of Iowa ophthalmology and primary care clinics included 100 patients with proliferative diabetic retinopathy (PDR), 100 patients with nonproliferative diabetic retinopathy (NPDR), 100 diabetic patients without diabetic retinopathy, and 100 nondiabetic patients who were randomly selected. Using the International Diabetes Foundation definition, the prevalence of metabolic syndrome and the number of components of metabolic syndrome were compared among these groups.
RESULTS: The prevalence of metabolic syndrome in patients with diabetes was 69.3%, which was significantly higher than that in patients without diabetes (27%; P<0.0001) (odds ratio [OR] =6.28; 95% confidence interval [CI]: 3.76-10.49; P=0.0004). However, there was no significant difference in the prevalence of metabolic syndrome between diabetics with and without diabetic retinopathy, with rates of 67.5% and 73%, respectively (P=0.36) (OR =0.77; 95% CI: 0.45-1.32; P=0.34). In addition, there was no significant difference between the PDR and NPDR groups, with rates of 63% and 72%, respectively (P=0.23) (OR =0.70; 95% CI: 0.38-1.30; P=0.26).
CONCLUSION: The metabolic syndrome was highly prevalent in patients with diabetes, but it was not associated with the presence or severity of retinopathy.
PMID: 25995613 [PubMed]
Quality of life in idiopathic intracranial hypertension at diagnosis: IIH Treatment Trial results.
Neurology. 2015 May 20;
Authors: Digre KB, Bruce BB, McDermott MP, Galetta KM, Balcer LJ, Wall M, NORDIC Idiopathic Intracranial Hypertension Study Group
OBJECTIVE: The study purpose was to examine vision-specific and overall health-related quality of life (QOL) at baseline in Idiopathic Intracranial Hypertension Treatment Trial patients who were newly diagnosed and had mild visual loss. We also sought to determine the associations between vision-specific QOL scores and visual symptoms, visual function, pain, headache-related disability, and obesity.
METHODS: We assessed QOL using the 36-Item Short Form Health Survey, National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25), and 10-Item NEI-VFQ-25 Neuro-Ophthalmic Supplement. We compared these results with those of previously reported idiopathic intracranial hypertension (IIH) QOL studies. We assessed relationships between QOL and other clinical characteristics.
RESULTS: Among 165 participants with IIH (161 women and 4 men with a mean age ± SD of 29.2 ± 7.5 years), vision-specific QOL scores were reduced compared with published values for disease-free controls. Scores of participants were comparable to published results for patients with multiple sclerosis and a history of optic neuritis. A multiple linear regression model for the NEI-VFQ-25 composite score found that perimetric mean deviation in the best eye, visual acuity in the worst eye, visual symptoms, and pain symptoms (headache, neck pain), but not obesity, were independently associated with QOL.
CONCLUSIONS: IIH affects QOL at time of diagnosis even in patients with mild visual impairment. Vision-specific QOL in patients with newly diagnosed IIH may be as decreased as that for patients with other neuro-ophthalmic disorders. IIH treatment should target visual loss and other symptoms of increased intracranial pressure associated with reduced QOL. Reduced QOL does not simply reflect obesity, an underlying IIH risk factor.
PMID: 25995055 [PubMed - as supplied by publisher]
CAPN5 mutation in hereditary uveitis: the R243L mutation increases calpain catalytic activity and triggers intraocular inflammation in a mouse model.
Hum Mol Genet. 2015 May 20;
Authors: Wert KJ, Bassuk AG, Wu WH, Gakhar L, Coglan D, Mahajan M, Wu S, Yang J, Lin CS, Tsang SH, Mahajan VB
A single amino acid mutation near the active site of the CAPN5 protease was linked to the inherited blinding disorder, ADNIV (OMIM #193235). In homology modeling with other calpains, this R243L CAPN5 mutation was situated in a mobile loop that gates substrate access to the calcium-regulated active site. In in vitro activity assays, the mutation increased calpain protease activity and made it far more active at low concentrations of calcium. To test whether the disease allele could yield an animal model of ADNIV, we created transgenic mice expressing human (h) CAPN5(R243L) only in the retina. The resulting hCAPN5(R243L) transgenic mice developed a phenotype consistent with human uveitis and ADNIV, at the clinical, histological, and molecular levels. The fundus of hCAPN5(R243L) mice showed enhanced autofluorescence and pigment changes indicative of reactive retinal pigment epithelial cells and photoreceptor degeneration. Electroretinography showed mutant mouse eyes had a selective loss of the b-wave indicating an inner-retina signaling defect. Histological analysis of mutant mouse eyes showed protein extravasation from dilated vessels into the anterior chamber and vitreous, vitreous inflammation, vitreous and retinal fibrosis, and retinal degeneration. Analysis of gene expression changes in the hCAPN5(R243L) mouse retina showed upregulation of several markers, including members of the Toll-like receptor pathway, chemokines, and cytokines, indicative of both an innate and adaptive immune response. Since many forms of uveitis share phenotypic characteristics of ADNIV, this mouse offers a model with therapeutic testing utility for ADNIV and uveitis patients.
PMID: 25994508 [PubMed - as supplied by publisher]
FSH receptor (FSHR) expression in human extragonadal reproductive tissues and the developing placenta, and the impact of its deletion on pregnancy in mice.
Biol Reprod. 2014 Sep;91(3):74
Authors: Stilley JA, Christensen DE, Dahlem KB, Guan R, Santillan DA, England SK, Al-Hendy A, Kirby PA, Segaloff DL
Expression and function of the follicle-stimulating hormone receptor (FSHR) in females were long thought to be limited to the ovary. Here, however, we identify extragonadal FSHR in both the human female reproductive tract and the placenta, and test its physiological relevance in mice. We show that in nonpregnant women FSHR is present on: endothelial cells of blood vessels in the endometrium, myometrium, and cervix; endometrial glands of the proliferative and secretory endometrium; cervical glands and the cervical stroma; and (at low levels) stromal cells and muscle fibers of the myometrium. In pregnant women, placental FSHR was detected as early as 8-10 wk of gestation and continued through term. It was expressed on: endothelial cells in fetal portions of the placenta and the umbilical cord; epithelial cells of the amnion; decidualized cells surrounding the maternal arteries in the maternal decidua; and the stromal cells and muscle fibers of the myometrium, with particularly strong expression at term. These findings suggest that FSHR expression is upregulated during decidualization and upregulated in myometrium as a function of pregnancy. The presence of FSHR in the placental vasculature suggests a role in placental angiogenesis. Analysis of genetically modified mice in which Fshr is lacking in fetal portions of the placenta revealed adverse effects on fetoplacental development. Our data further demonstrate FSHB and CGA mRNAs in placenta and uterus, consistent with potential local sources of FSH. Collectively, our data suggest heretofore unappreciated roles of extragonadal FSHR in female reproductive physiology.
PMID: 25100706 [PubMed - indexed for MEDLINE]