Search

Müller cells are the major glial cells spanning the entire layer of the retina and maintaining retinal structure. Under pathological conditions, Müller cells are involved in retinal angiogenesis, a process of growing new blood vessels from pre-existing capillaries. In response to hypoxia, high glucose, and inflammation conditions, multiple signaling pathways are activated in Müller cells, followed by the increased production of proangiogenic factors including vascular endothelial growth factor, basic fibroblast growth factor, matrix metalloproteinases, Netrin-4, and angiopoietin-like 4. Expression of antiangiogenic factors is also downregulated in Müller cells. Besides, proliferation and dedifferentiation of Müller cells facilitates retinal angiogenesis. In this review, we summarized molecular mechanisms of Müller cells-related retinal angiogenesis. The potential of Müller cells as a therapeutic target for retinal angiogenesis was also discussed. [ABSTRACT FROM AUTHOR]

The etiology of heritable diseases may be elucidated by localizing genes conferring susceptibility and by subsequent biological characterization of these genes. To localize genetic components for multifactorial traits, both hypothesis-driven candidate gene and hypothesis-free genome scan approaches have been applied. To date, only a handful of results have been reproduced in either a different cohort or model organisms. The integration of genetic approaches with high-throughput genomic techniques is very promising. Unfortunately, most genetic studies completely ignore strong nongenetic effects such as low education and poverty even though these factors are well-known to predict, for example, obesity. Thus, what are most needed in future research are statistical methods for discovering sets of susceptibility genes and environmental factors, as well as systematic verifications of the gene–environment–disease network. [Copyright &y& Elsevier]

The discovery of strong associations of the His402 variant of complement factor H (CFH) and the change in the promoter region of HtrA serine peptidase 1 (HTRA1) with age-related macular degeneration (AMD) have altered our conception of the pathophysiology of this disease. The complement system has been placed at the center of a flurry of research interest, and a similar growth in attention to the serine proteases is not far behind. The specific role of these variants in causing AMD is unknown, but they will undoubtedly lead to a deeper understanding of the biological mechanisms and will point to new avenues for pharmacologic management. Furthermore, these variants will enable clinicians and investigators to identify people at high risk for this condition, thereby establishing the preconditions for preventing the disease. [Copyright &y& Elsevier]

The integration of the many roles of mitochondria in cellular function and the contribution of mitochondrial dysfunction to disease are major areas of research. Within this realm, the roles of mitochondria in immune defense, epigenetics, and stem cell (SC) development have recently come into the spotlight. With new understanding, mitochondria may bring together these seemingly unrelated fields, a crucial process in treatment and prevention for various diseases. In this review we describe novel findings in these three arenas, discussing the significance of the interplay between mitochondria and the cell nucleus in response to environmental cues. While we optimistically anticipate that further research in these areas can have a profound impact on disease management, we also bring forth some of the key questions and challenges that remain. [ABSTRACT FROM AUTHOR]

Abstract: Asthma is a chronic inflammatory disease of the lungs which affects more than 6.5 million American children. A family-based genome-wide association study of copy-number variation identified an association between decreased copy-number at TCRγ and childhood allergic asthma. TCRγ encodes the T-cell receptor gamma glycoprotein, a cell-surface protein found on T-cells and involved in cell-mediated immunity. Using quantitative real-time PCR, we sought to determine if copy-number variation at TCRα, TCRβ or TCRγ was associated with childhood allergic asthma in an independent cohort of 94 cases and 455 controls using DNA from buccal swabs. Copy-number variation at these loci is well-known, but appears to be dominated by somatic mutations. Genotyping results indicated that copy-number variants at these genes are largely somatic mutations, as inheritance did not show Mendelian consistency. In these mosaic cell populations, copy-number was significantly reduced among asthmatic children at TCRγ (p =0.0199), but was not associated at TCRα or TCRβ (p =0.7972 and 0.8585, respectively). These findings support the association between reduced copy-number at TCRγ and childhood allergic asthma. Further work is needed to resolve whether reduced copy-number at TCRγ predisposes individuals to asthma, or whether deletion of this gene is a somatic response to the disease. [ABSTRACT FROM AUTHOR]

Abstract: Age-related macular degeneration (AMD) is a complex disorder with genetic and environmental influences. The genetic influences affecting AMD are not well understood and few genes have been consistently implicated and replicated for this disease. A polymorphism (rs11200638) in a transcription factor binding site of the HTRA1 gene has been described, in previous reports, as being most significantly associated with AMD. In this paper, we investigate haplotype association and individual polymorphic association by genotyping additional variants in the AMD risk-associated region of chromosome 10q26. We demonstrate that rs11200638 in the promoter region and rs2293870 in exon 1 of HTRA1, are among the most significantly associated variants for advanced forms of AMD. [Copyright &y& Elsevier]