Lipids an Age-related Macular Degeneration

Given the considerable public health burden imposed by age-related macular degeneration (AMD), much effort has been directed towards elucidating principles of pathogenesis in order to identify risk factors and develop preventive measures and treatments. Together with epidemiological evidence linking cardiovascular risk factors with AMD risk and basic science work examining the role of lipid metabolism in AMD, numerous human studies have assayed a potential relationship between dietary lipids and the development of AMD. We examine the evidence for a role for lipid metabolism in AMD, highlighting key basic biochemical principles, work in animal models, and relevant human studies. the topics of lipoprotein modulation and omega-3 fatty acid intake receive special attention from both a basic science and clinical study standpoint. the evidence suggests that consumption of omega-3 fatty acids, perhaps in concert with antioxidants, may constitute a rational preventative strategy against AMD development, though, absent an appropriately developed double-blind, randomized control trial, insufficient data exist to recommend implementation in the clinical setting at this time. (Surv Ophthalmol 56:195-213, 2011. (C) 2011 Elsevier Inc. All rights reserved.)UC Davis Eye Ctr, Sacramento, CA 95817 USAHarvard Univ, Sch Med, Boston, MA USAUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilWeb of Scienc

Comparison of In Vivo

Purpose. To identify retinal pigment epithelium (RPE)/choroid genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. Methods. Differential gene expression of over 34,000 well-characterized mouse genes in the RPE/choroid of 6-week-old C57BL/6J mice was analyzed after intravitreal steroid injections at 1 week and 1 month postinjection, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpring GX 12.5 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes. Results. Both triamcinolone and dexamethasone caused differential activation of genes involved in “Circadian Rhythm Signaling” pathway at both time points tested. Triamcinolone (TAA) uniquely induced significant changes in gene expression in “Calcium Signaling” (1 week) and “Glutamate Receptor Signaling” pathways (1 month). In contrast, dexamethasone (Dex) affected the “GABA Receptor Signaling” (1 week) and “Serotonin Receptor Signaling” (1 month) pathways. Understanding how intraocular steroids affect the gene expression of RPE/choroid is clinically relevant. Conclusions. This in vivo study has elucidated several genes and pathways that are potentially altering the circadian rhythms and several other neurotransmitter pathways in RPE/choroid during intravitreal steroid injections, which likely has consequences in the dysregulation of RPE function and neurodegeneration of the retina

Unique molecular signatures of microRNAs in ocular fluids and plasma in diabetic retinopathy.

The main objective of this pilot study was to identify circulatory microRNAs in aqueous or plasma that were reflecting changes in vitreous of diabetic retinopathy patients. Aqueous, vitreous and plasma samples were collected from a total of 27 patients undergoing vitreoretinal surgery: 11 controls (macular pucker or macular hole patients) and 16 with diabetes mellitus(DM): DM-Type I with proliferative diabetic retinopathy(PDR) (DMI-PDR), DM Type II with PDR(DMII-PDR) and DM Type II with nonproliferative DR(DMII-NPDR). MicroRNAs were isolated using Qiagen microRNeasy kit, quantified on BioAnalyzer, and profiled on Affymetrix GeneChip miRNA 3.0 microarrays. Data were analyzed using Expression Console, Transcriptome Analysis Console, and Ingenuity Pathway Analysis. The comparison analysis of circulatory microRNAs showed that out of a total of 847 human microRNA probes on the microarrays, common microRNAs present both in aqueous and vitreous were identified, and a large number of unique microRNA, dependent on the DM type and severity of retinopathy. Most of the dysregulated microRNAs in aqueous and vitreous of DM patients were upregulated, while in plasma, they were downregulated. Dysregulation of miRNAs in aqueous did not appear to be a good representative of the miRNA abundance in vitreous, or plasma, although a few potential candidates for common biomarkers stood out: let-7b, miR-320b, miR-762 and miR-4488. Additionally, each of the DR subtypes showed miRNAs that were uniquely dysregulated in each fluid (i.e. aqueous: for DMII-NPDR was miR-455-3p; for DMII-PDR was miR-296, and for DMI-PDR it was miR-3202). Pathway analysis identified TGF-beta and VEGF pathways affected. The comparative profiling of circulatory miRNAs showed that a small number of them displayed differential presence in diabetic retinopathy vs. controls. A pattern is emerging of unique molecular microRNA signatures in bodily fluids of DR subtypes, offering promise for the use of ocular fluids and plasma for diagnostic and therapeutic purposes