ABSTRACT
Mouse models of age-related macular degeneration (AMD) such as Ccl2-/- and Ccl2-/-/Cx3cr1-/- have not yet been fully characterized ultrastructurally. Although we have previously shown extranuclear DNA (enDNA) leakage into the cytoplasm and damaged mitochondria in the retinal pigment epithelium (RPE) of these AMD mouse models, little is known about the state of their vascular capillaries of the retina and choroid. Our ultrastructural survey shows that the aberrations were not restricted to the RPE cells, but also extended to the vasculature of the retina and choroid. Their endothelial aberrations included cytoplasmic degeneration, pyknotic DNA, hypertrophic nuclei, and loss of fenestration in addition to duplication of basement membrane and loss of density in Bruch's membrane. Moreover, the state of the vasculature in the mutant mice models suggests that the capillaries could also be active contributors to the pathological findings seen in AMD. The goal of this study is to gain insights into the early events of AMD that may lead to a better understanding of AMD's pathogenesis, improve our preventative measures, and formulate designed therapeutic regimens that are tailored to target the initial pathological events.Abbreviations: AMD: age-related macular degeneration; BM: Bruch's membrane; DPC: degenerate pericyte; EN: endothelial nucleus; enDNA: extranuclear DNA; GCL: ganglion cell layer; HEN: hypertrophic endothelial nucleus; IPL: inner plexiform layer; NFL: nerve fiber layer; OPL: outer plexiform layer; RBC: red blood cell; RPE: retinal pigment epithelium; SNPs: Single nucleotide polymorphisms.
Subject(s)
Capillaries/pathology , Choroid/pathology , Macular Degeneration/pathology , Retina/pathology , Animals , Capillaries/ultrastructure , Choroid/ultrastructure , Disease Models, Animal , Mice , Mice, Inbred C57BL , Mice, Knockout , Microscopy, Electron, Transmission , Phenotype , Retina/ultrastructureABSTRACT
We present the case of a 31-year-old female with a past medical history of B-cell leukemia, on maintenance chemotherapy administered via centrally placed implantable catheter port, who presented to the emergency room with fever, chills, and generalized body pain of one day's duration. After initial workup, the patient was admitted to the intensive care unit and managed for severe sepsis. The patient was found to have a new-onset 3/6 holosystolic murmur at the left lower sternal border. Furthermore, she developed an episode of supraventricular tachycardia that responded to adenosine. Transthoracic echocardiogram revealed severe tricuspid regurgitation but without valvular vegetation. Transesophageal echocardiogram further confirmed the absence of vegetation, in addition to visualizing the tip of the catheter tip in the right atrium and interfering with coaptation of the tricuspid valve. It was postulated that the severe tricuspid regurgitation and supraventricular tachycardia were caused by the catheter tip malposition. The catheter was subsequently removed. The patient's acute condition resolved and she was referred to cardiothoracic surgery for valvular surgery.
