597 research outputs found

    Induced pluripotent stem cell-based therapy for age-related macular degeneration

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    Introduction: In age-related macular degeneration (AMD), stem cells could possibly replace or regenerate disrupted pathologic retinal pigment epithelium (RPE), and produce supportive growth factors and cytokines such as brain-derived neurotrophic factor. Induced pluripotent stem cells (iPSCs)-derived RPE was first subretinally transplanted in a neovascular AMD patient in 2014. Areas covered: Induced PSCs are derived from the introduction of transcription factors to adult cells under specific cell culture conditions, followed by differentiation into RPE cells. Induced PSC-derived RPE cells exhibit ion transport, membrane potential, polarized VEGF secretion and gene expression that is similar to native RPE. Despite having similar in vitro function, morphology, immunostaining and microscopic analysis, it remains to be seen if iPSC-derived RPE can replicate the myriad of in vivo functions, including immunomodulatory effects, of native RPE cells. Historically, adjuvant RPE transplantation during CNV resections were technically difficult and complicated by immune rejection. Autologous iPSCs are hypothesized to reduce the risk of immune rejection, but their production is time-consuming and expensive. Alternatively, allogenic transplantation using human leukocyte antigen (HLA)-matched iPSCs, similar to HLA-matched organ transplantation, is currently being investigated. Expert opinion: Challenges to successful transplantation with iPSCs include surgical technique, a pathologic subretinal microenvironment, possible immune rejection, and complications of immunosuppression

    Combat and Warfare in the Early Paleolithic and Medically Unexplained Musculo-Facial Pain in the 21st Century War Veterns and Active-Duty Military Personnel

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    In a series of recent articles, we suggest that family dentists, military dentists and psychiatrists with expertise in posttraumatic stress disorder (especially in the Veterans Health Administration) are likely to see an increased number of patients with symptomatic jaw-clenching and early stages of tooth- grinding (Bracha et al., 2005). Returning warfighters and other returnees from military deployment may be especially at risk for high rates of clenching- induced masticatory muscle disorders at early stages of incisor grinding. The literature we have recently reviewed strongly supports the conclusion that clenching and grinding may primarily be a manifestation of experiencing extreme fear or severe chronic distress (respectively). We have recently reviewed the clinical and paleoanthropological literature and have noted that ancestral warfare and ancestral combat, in the early Paleolithic Environment of Evolutionary Adaptedness (EEA) may be a neglected factor explaining the conservation of the archaic trait of bite-muscle strengthening. We have hypothesized that among ancestral warriors, jaw clenching may have rapidly strengthened the two primary muscles involved in biting, the masseter muscles and the much larger temporalis muscles. The strengthening of these muscles may have served the purpose of enabling a stronger, deeper, and therefore more lethal, defensive bite for early Paleolithic humans. The neuroevolutionary perspective presented here may be novel to many dentists. However, it may be useful in patient education and in preventing progression from jaw-clenching to chronic facial pain

    Gene Therapy for Inherited Retinal and Optic Nerve Degenerations

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    Introduction: The eye is a target for investigational gene therapy due to the monogenic nature of many inherited retinal and optic nerve degenerations (IRD), its accessibility, tight blood-ocular barrier, the ability to non-invasively monitor for functional and anatomic outcomes, as well as its relative immune privileged state.Vectors currently used in IRD clinical trials include adeno-associated virus (AAV), small single-stranded DNA viruses, and lentivirus, RNA viruses of the retrovirus family. Both can transduce non-dividing cells, but AAV are non-integrating, while lentivirus integrate into the host cell genome, and have a larger transgene capacity. Areas covered: This review covers Leber’s congenital amaurosis, choroideremia, retinitis pigmentosa, Usher syndrome, Stargardt disease, Leber’s hereditary optic neuropathy, Achromatopsia, and X-linked retinoschisis. Expert opinion: Despite great potential, gene therapy for IRD raises many questions, including the potential for less invasive intravitreal versus subretinal delivery, efficacy, safety, and longevity of response, as well as acceptance of novel study endpoints by regulatory bodies, patients, clinicians, and payers. Also, ultimate adoption of gene therapy for IRD will require widespread genetic screening to identify and diagnose patients based on genotype instead of phenotype

    Vital Dyes in Vitreomacular Surgery

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    Vital dyes contain complex molecules with chromophores that stain living tissues and have greatly enhanced identification and removal of transparent vitreoretinal tissues during surgery. Several “chromovitrectomy” dyes are frequently used by vitreoretinal specialists, including indocyanine green, trypan blue, brilliant blue G, and triamcinolone acetonide; other dyes are also under investigation. Trypan Blue was approved by the U.S. Food and Drug Administration (FDA) for epiretinal membrane removal, and preservative-free triamcinolone acetonide was approved by the FDA for intraocular use. However, currently available chromovitrectomy dyes have their limitations, and of particular concern for some of them is the possibility for acute and chronic toxicity to the neurosensory retina and retinal pigmented epithelium. The potentially irreversible acute toxicity and other limitations, such as lack of long-term safety profiles, highlight the need for further advancements

    A Child with X-Linked Agammaglobulinemia and Enthesitis-Related Arthritis

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    X-linked agammaglobulinemia (XLA) is a primary immune deficiency characterized by recurrent bacterial infections and profoundly depressed serum immunoglobulin levels and circulating mature B cells. We describe a 12-year-old boy with XLA and enthesitis-related arthritis (ERA). To date, there has been a paucity of reports of noninfectious inflammatory arthritis in children with XLA. This case illustrates that functional B cells and/or immunoglobulin are not required for ERA pathogenesis. In addition, this case suggests a possible link between immune deficiency, immune dysregulation, and rheumatic illness

    The acute and chronic effects of intravitreal anti-vascular endothelial growth factor injections on intraocular pressure: A review

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    The acute and chronic effects of repeated intravitreal antivascular endothelial growth factor (VEGF) injections on intraocular pressure have not been fully characterized, and the development of sustained ocular hypertension could adversely affect patients who are at risk of glaucomatous optic neuropathy. As expected, volume-driven, acute ocular hypertension immediately follows intravitreal injection, but this pressure elevation is generally transient and well tolerated. Several medications have been investigated to limit acute ocular hypertension following anti-VEGF therapy, but the benefits of pretreatment are not conclusive. Chronic, sustained ocular hypertension, distinct from the short-term acute ocular hypertension after each injection, has also been associated with repeated intravitreal anti-VEGF injections. Risk factors for chronic ocular hypertension include the total number of injections, a greater frequency of injection, and preexisting glaucoma. Proposed mechanisms for chronic ocular hypertension include microparticle obstruction, toxic or inflammatory effects on trabecular meshwork, as well as alterations in outflow facility by anti-VEGF agents. Although limiting anti-VEGF therapy could minimize the risk of both acute and chronic ocular hypertension, foregoing anti-VEGF therapy risks progression of various macular diseases with resulting permanent central vision loss. While definitive evidence of damage to the retinal nerve fiber layer is lacking, patients receiving repeated injections should be monitored for ocular hypertension and patients in whom sustained ocular hypertension subsequently developed should be periodically monitored for glaucomatous changes with optic nerve optical coherence tomography and static visual fields

    Intraorbital neuromuscular choristoma adjacent to the optic nerve

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    AbstractNeuromuscular choristoma is a rare tumor that incorporates mature skeletal muscle within fascicles of peripheral nerve. The etiology is poorly understood, yet most present in large nerves of children, with a tight link to post-operative fibromatosis recently appreciated. Herein, we report an exceptional intra-orbital example in a 53-year-old man with optic nerve compression
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