Retinal neurodegeneration is predominantly reported as the apoptosis or impaired function of the photoreceptors. Retinal degeneration is a major causative factor of irreversible vision loss leading to blindness. In recent years, retinal degenerative diseases have been investigated and many genes and genetic defects have been elucidated by many of the causative factors. An enormous amount of research has been performed to determine the pathogenesis of retinal degenerative conditions and to formulate the treatment modalities that are the critical requirements in this current scenario. Encouraging results have been obtained using gene therapy. We provide a narrative review of the various studies performed to date on the role of inflammation in human retinal degenerative diseases such as age-related macular degeneration, inherited retinal dystrophies, retinitis pigmentosa, Stargardt macular dystrophy, and Leber congenital amaurosis. In addition, we have highlighted the pivotal role of various inflammatory mechanisms in the progress of retinal degeneration. This review also offers an assessment of various therapeutic approaches, including gene-therapies and stem-cell-based therapies, for degenerative retinal diseases.
Pathological retinal neovascularization (NV) is a clinical manifestation of various proliferative retinopathies, and treatment of NV using anti-VEGF therapies is not selective, as it also impairs normal retinal vascular growth and function. Here, we show that genetic deletion or siRNA-mediated downregulation of IL-33 reduces pathological NV in a murine model of oxygen-induced retinopathy (OIR) with no effect on the normal retinal repair. Furthermore, our fluorescent activated cell sorting (FACS) data reveals that the increase in IL-33 expression is in endothelial cells (ECs) of the hypoxic retina and conditional genetic deletion of IL-33 in retinal ECs reduces pathological NV. In vitro studies using human retinal microvascular endothelial cells (HRMVECs) show that IL-33 induces sprouting angiogenesis and requires NFkappaB-mediated Jagged1 expression and Notch1 activation. Our data also suggest that IL-33 enhances de-ubiquitination and stabilization of Notch1 intracellular domain via its interaction with BRCA1-associated protein 1 (BAP1) and Numb in HRMVECs and a murine model of OIR.
Vision is an ability that depends on the precise structure and functioning of the retina. Any kind of stress or injury can disrupt the retinal architecture and leads to vision impairment, vision loss, and blindness. Immune system and immune response function maintain homeostasis in the microenvironment. Several genetic, metabolic, and environmental factors may alter retinal homeostasis, and these events may initiate various inflammatory cascades. The prolonged inflammatory state may contribute to the initiation and development of retinal disorders such as glaucoma, age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa, which pose a threat to vision. In the current review, we attempted to provide sufficient evidence on the role of inflammation in these retinal disorders. Moreover, this review paves the way to focus on therapeutic targets of the disease, which are found to be promising.
This paper presents an exercise to demonstrate the benefits of hardware/software codesign. A RISC processor and a high-level language have been designed together to make best use of the features of one another. A CPU simulator, an assembler and a compiler have been implemented based on the design. The exercise is suitable for students of computer engineering and electronics engineering students nearing their graduation. ß 2015 Wiley Periodicals, Inc. Comput Appl Eng Educ 24:305-312, 2016; View this article online at wileyonlinelibrary. com/journal/cae;
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