The functional role of decorin in corneal neovascularization in vivo.

Our earlier decorin (Dcn) gene overexpression studies found that the targeted Dcn gene transfer into the cornea inhibited corneal angiogenesis in vivo using a rabbit model. In this study, we tested the hypothesis that anti-angiogenic effects of decorin in the cornea are mediated by alterations in a normal physiologic balance of pro- and anti-angiogenic factors using decorin deficient (Dcn-/-) and wild type (Dcn+/+) mice. Corneal neovascularization (CNV) in Dcn-/- and Dcn+/+ mice was produced with a standard chemical injury technique. The clinical progression of CNV in mice was monitored with stereo- and slit-lamp microscopes, and histopathological hematoxylin and eosin (H&E) staining. Protein and mRNA expression of pro- and anti-angiogenic factors in the cornea were evaluated using immunofluorescence and quantitative real-time PCR, respectively. Slit-lamp clinical eye examinations revealed significantly more CNV in Dcn-/- mice than the Dcn+/+ mice post-injury (p < 0.05) and AAV5-Dcn gene therapy significantly reduced CNV in Dcn-/- mice compered to no AAV5-Dcn gene therapy controls (p < 0.001). H&E-stained corneal sections exhibited morphology with several neovessels in injured corneas of the Dcn-/- mice than the Dcn+/+ mice. Immunofluorescence of corneal sections displayed significantly higher expression of α-smooth muscle actin (α-SMA) and endoglin proteins in Dcn-/- mice than Dcn+/+ mice (p < 0.05). Quantitative real-time PCR found significantly increased mRNA levels of pro-angiogenic factors endoglin (2.53-fold; p < 0.05), Vegf (2.47-fold; p < 0.05), and Pecam (2.14-fold; p < 0.05) and anti-angiogenic factor Vegfr2 (1.56-fold; p < 0.05) in the normal cornea of the Dcn-/- mice than the Dcn+/+ mice. Furthermore, neovascularized Dcn-/- mice corneas showed greater increase in mRNA expression of pro-angiogenic factors endoglin (4.58-fold; p < 0.0001), Vegf (4.16-fold; p < 0.0001), and Pdgf (2.15-fold; p < 0.0001) and reduced expression of anti-angiogenic factors Ang2 (0.12-fold; p < 0.05), Timp1 (0.22-fold; p < 0.05), and Vegfr2 (0.67-fold; p > 0.05) compared to neovascularized Dcn+/+ mice corneas. These gene deficience studies carried with transgenic Dcn-/- mice revealed decorin's role in influencing a physiologic balance between pro-and anti-angiogenic factors in the normal and injured cornea. We infer that the functional deletion of Dcn promotes irregular corneal repair and aggravates CNV.

Relationship between novel inflammatory biomarker galectin-3 and depression symptom severity in a large community-based sample.

Major depressive disorder is associated with pro-inflammatory markers, such as cytokines TNF-alpha, IL-6, IL-1ß, and C-reactive protein. Galectin-3 is a novel emerging biomarker with pro-inflammatory properties. It is a saccharide binding protein distributed throughout many tissues with varying functions and is a predictor of poor outcomes in patients with heart failure and stroke. However, its role as a predictor in depressive symptom severity remains undefined. Data from the community-based Dallas Heart Study (n = 2554) were examined using a multiple linear regression analysis to evaluate the relationship between galectin-3 and depressive symptom severity as assessed with Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) scores. Additional covariates included age, sex, race/ethnicity, body mass index (BMI), years of education, serum creatinine, history of diabetes, and smoking history. Galectin-3 levels statistically significantly predicted QIDS-SR depressive symptom severity (ß = 0.055, p = .015). Female sex, smoking status, and BMI were found to be statistically significant positive predictors of depression severity, while age, years of education, non-Hispanic White race, and Hispanic ethnicity were negative predictors of depressive symptom severity. In this large sample, higher galectin-3 levels were associated with higher levels of depressive symptoms. The findings suggest that galectin-3 may be a new and useful inflammatory biomarker associated with depression.