Exfoliation syndrome (XFS) is the commonest known risk factor for secondary glaucoma and a significant cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A have been previously associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results between populations, and to identify new variants associated with XFS. We identified a rare, protective allele at LOXL1 (p.407Phe, OR = 25, P =2.9 × 10−14) through deep resequencing of XFS cases and controls from 9 countries. This variant results in increased cellular adhesion strength compared to the wild-type (p.407Tyr) allele. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10−8). Index variants at the new loci map to chromosomes 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS, and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.
ngiolymphoid hyperplasia with eosinophilia (ALHE), also known as epithelioid hemangioma, is a rare, benign disorder characterized by marked vascular proliferation and inflammation. The usual sites of involvement are the subcutaneous tissues of the head and neck. Involvement of the ocular adnexa, including the orbits, has also been reported in the literature. 1,2 Similar to many tumors that involve the ocular adnexa or orbit, the presenting signs, symptoms, and radiologic findings in ALHE are nonspecific; therefore, histologic evaluation is essential in making the diagnosis. We report the clinical (Figure 1) and histopathologic (Figure 2) findings in 5 patients with ocular adnexal ALHE who presented to us in a 20-year period. Thirty-six cases of ALHE in 21 reports with orbital and ocular adnexal involvement have been reported previously in the literature. To our knowledge, the current report is the largest case series reported in the literature.
Report of CasesFive patients (3 men and 2 women) had ALHE diagnosed at a range of 11 to 86 years. The clinical and histopathologic characteristics of the patients are summarized in the Table . In all 5 patients, ALHE presented unilaterally with eyelid swelling.
The objective of this study was to determine whether resveratrol or a defined, reconstituted grape powder can attenuate the formation of new blood vessels in a mouse model of choroidal neovascularization (CNV). To accomplish this objective, C57BL/6J mice were randomized into control or treatment groups which received either resveratrol or grape powder by daily oral gavage, resveratrol or grape powder delivered ad libitum through the drinking water, or resveratrol by slow release via implanted osmotic pumps. A laser was used to rupture Bruch’s membrane to induce CNV which was then detected in sclerochoroidal eyecups stained with antibodies against intercellular adhesion molecule-2. CNV area was measured using fluorescence microscopy and Image J software. Ad libitum delivery of both resveratrol and grape powder was shown to significantly reduce the extent of CNV by 68% and 57%, respectively. Parallel experiments conducted in vitro demonstrated that resveratrol activates p53 and inactivates Akt/protein kinase B in choroidal endothelial cells, contributing to its anti-proliferative and anti-migratory properties. In addition resveratrol was shown to inhibit the formation of endothelial cell networks, augmenting its overall anti-angiogenic effects. The non-toxic nature of resveratrol makes it an especially attractive candidate for the prevention and/or treatment of CNV.
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