Ординатура / Офтальмология / Английские материалы / Retinal and Choroidal Angiogenesis_Penn_2008

improved techniques for both diagnostics and local and systemic drug delivery to the CNV in AMD in the future.66

5.CONCLUSION

Several molecules including VEGF, MMP and PEDF, as well as breakdown of the blood-retina barrier comprising RPE and Bruch’s membrane, seem to be implicated in the process preceding the development of CNV in AMD. Many signs of an inflammatory response are present, and CNV is similar in many ways to a nonspecific wound healing process. Combination therapies targeting these multifactor processes hold promise for future treatment of

CNV in AMD. Several excellent reviews have been published

recently.7,50,67,68

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GLOSSARY

ablation. The removal of tissue by cutting or laser photo-destruction. acellular capillaries. A hollow basement membrane, through which blood

no longer flows, left behind when cellular elements of a capillary die. acromegaly. A disorder caused by chronic overproduction of growth

hormone by the pituitary gland and characterized by a gradual and permanent enlargement of the lower jaw, hands and feet, and other body parts.

acuity. Keenness of visual perception.

adenosine. A nucleoside constituent of RNA and DNA that also acts as a signaling molecule.

age-related macular degeneration (AMD or ARMD). Progressive deterioration of the macular region of the retina resulting in a gradual loss of the central part of the field of vision, especially affecting the elderly in either a slowly progressing form marked by the accumulation of yellow deposits in the macula lutea or in a rapidly progressing form marked by scarring of the macula lutea.

agonist. A molecule capable of binding to a receptor on a cell and initiating the same reaction or activity typically produced by the binding of an endogenous ligand.

anastomosis. Coalescence or surgical union of blood vessels.

angioblast. An extraembryonic mesenchymal cell that differentiates into the endothelium of embryonic blood vessels.

angiogenesis. The formation of new blood vessels from the pre-existing vasculature.

angiography. The radiographic visualization of blood vessels after injection of a detectable substance.

anoxic. Without oxygen.

antagonist. A ligand that inhibits the function of an agonist or inverse agonist for a specific receptor.

aptamer. A short oligomer of nucleotides or sometimes amino acids used to bind another biomolecule, usually to inhibit its function.

aqueous humor. The transparent fluid occupying the space between the lens and the cornea of the eye.

545

astrocyte. A star-shaped glial cell within the retina that promotes retinal vascular development and reinforces the blood-retina barrier.

basement membrane. The thin layer of extracellular matrix upon which is posed a single layer of epithelial or endothelial cells.

blood-retina barrier. Closely spaced and junctionally-complexed endothelial cells lining the retinal capillary lumen. This limits the diffusion of molecules from the bloodstream to the retina.

cannula. A small tube for insertion into a body cavity, duct, or vessel. capillary. Any of the smallest blood vessels connecting arterioles with

venules and responsible for transferring the majority of oxygen from the blood to the surrounding tissues.

carbogen. A gas mixture of carbon dioxide (5%) and oxygen (95%) that has been used clinically, in place of 100% oxygen, to minimize the vasoconstrictive effects of pure O2 on retinal blood flow.

choriocapillaris. The innermost of the vascular layers of the choroid, composed largely of capillaries.

choroid. A vascular membrane containing large branched pigmented cells, and lying between the retina and the sclera of the eye.

conjunctiva. The mucous membrane that covers the exposed portion of the eyeball and lines the inner surface of the eyelids.

depot. A location within the body where a substance is stored, usually for utilization at some point in the future.

diabetes. A variable disorder of carbohydrate metabolism characterized by inadequate secretion or utilization of insulin. Diabetes causes decreased blood flow in the retina, which leads to the neovascularization that characterizes diabetic retinopathy.

dilatation. The condition of being stretched beyond normal dimensions, especially as a result of overwork or disease.

drusen. Small yellowish deposits of cellular debris that accumulate between the pigmented epithelial layer of the retina and the inner collagenous layer of the choroid.

endothelial cell. One of a single layer of thin, flattened cells that lines blood vessels and internal body cavities.

ephrin. A membrane-bound or transmembrane cell surface protein that binds to the Eph class of receptor tyrosine kinases and facilitates blood vessel formation during embryogenesis and adult neovascularization.

euglycemia. Normal level of glucose in the blood.

extracellular matrix (ECM). That portion of tissue not comprised of cellular constituents. It is composed mainly of glycoproteins, proteoglycans, and hyaluronic acid and sequesters many growth factors that are released upon ECM breakdown.

extravasation. The process of passing by infiltration or effusion from a proper vessel or channel (as a blood vessel) into surrounding tissue.

fenestration. A natural or surgically created opening in a surface (for example, of a blood vessel).

fluorescein. A highly fluorescent molecule commonly used in microscopy to visualize blood vessels. Often derivatized as fluorescein isothiocyanate (FITC).

fovea. A small rodless region of the retina that affords acute vision.

fundus. The inner back lining of the eye, opposite the pupil, containing structures crucial for processing visual images.

ganglion cell. A nerve cell having its body outside the central nervous system.

gavage. Introduction of material into the stomach by a tube.

gestation. The carrying of young in the uterus from conception to delivery; the time during which gestation takes place.

glial cell. Cells that surround neural tissue and are responsible for maintaining a specific environment for the neurons by adjusting ion, nutrient, and protein levels. In the retina, Müller cells and astrocytes.

glycosaminoglycans. Polysaccharides containing amino sugars and often forming complexes with proteins. They are constituents of mucoproteins, glycoproteins, and blood-group substances.

growth factor. A substance that promotes cellular growth, differentiation, proliferation, or survival.

hematopoietic stem cell (HSC). A stem cell originating in the bone marrow and giving rise to cells of many different types including blood and immune cells.

histology. Tissue structure and organization. hyperglycemia. Excess sugar in the blood. hyperopia. Farsightedness.

hyperoxia. Increased amount of oxygen reaching the tissues of the body. hypoxia. A deficiency of oxygen reaching the tissues of the body. hypoxia-inducible factor (HIF). A heterodimeric transcription factor that,

in response to hypoxia, translocates to the nucleus and upregulates the transcription of VEGF and other hypoxia-inducible gene products.

integrin. A heterodimeric glycoprotein found on cell surfaces that typically contains an Arg-Gly-Asp binding sequence; it promotes cellular adhesion during various biological processes such as phagocytosis and angiogenesis.

intussusception. Assimilation of new substances into the existing components of living tissue.

ischemia. Local deficiency of blood supply produced by vasoconstriction, local obstacles to the arterial flow, or absence of vessel patency.

lavage. Cleansing an organ, such as they eye, by irrigation.

macula. The central, avascular region of the retina located at the posterior pole and containing the fovea. The macula contains a dense concentration of cone photoreceptor cells that help us with fine visual detail and color vision.

matrix metalloproteinases (MMPs). Proteinases that degrade the extracellular matrix, thus facilitating cell migration and angiogenesis.

modality. A physical means of providing therapeutic treatment.

model. A system used to study processes that take place in humans or other living organisms. These systems can be used in medical research in order to understand human disease processes.

Müller cell. Glial fibers that extend throughout much of the thickness of the retina, acting as support for the other structures.

myopia. A condition in which visual images are focused in front of the retina. This is often due to a defective lens or an abnormally long eyeball,

resulting especially in defective vision of distant objects; also called nearsightedness.

neovascularization. New blood vessel formation in abnormal tissues, positions, or quantities; pathological angiogenesis.

neuron. One of the cells that constitute nervous tissue and that has the property of receiving and transmitting nervous impulses.

nonproliferative retinopathy. An early stage of retinopathy that includes capillary cell death and capillary atrophy, microaneurysms, pericyte loss, and increased vascular permeability, but not the expansion of the blood vessel network.

nystagmus. A persistent, rapid, involuntary side-to-side eye movement. occlusion. An obstruction of something, e.g., a blood vessel.

ocular. Of or relating to the eye.

ophthalmology. The branch of medical science dealing with the structure, functions, and diseases of the eye.

ora serrata. The anterior dentate (having teeth or pointed projections) border of the retina.

oxygen-induced retinopathy (OIR). Experimentally induced retinopathy resulting from retinal ischemia-induced hypoxia during retinal vascular development.

papilla. A small projection. In the eye, the slight elevation that is produced by the bundled optic nerve fibers entering the eyeball.

parenteral. Inside the body, but outside the intestine. Taken into the body in a manner other than through the digestive canal.

pathogenesis. The origin and development of a disease.

pathology. Physiological deviations from the normal that constitute disease or characterize a particular disease.

perfuse. To flush or spread over or through in the manner of a fluid and especially blood; to force a fluid through (an organ or tissue), especially by way of the blood vessels.

pericyte. A connective tissue cell intimately associated with capillaries or other small blood vessels, providing them support.

peripheral. Relating to the outer part of the retina or visual field. photoreceptor. Retinal cell that responds to light stimuli. Photoreceptors

consist of rod cells and cone cells, which are involved in low-light vision and color vision, respectively.

pigment epithelium-derived factor (PEDF). A potent endogenous angiostatic factor first isolated from RPE-conditioned growth medium. progenitor cell. A cell that precedes another in the pathway of

differentiation from a stem cell to a fully specialized cell.

proliferative retinopathy. The later stage of diabetic retinopathy characterized by neovascularization.

protein kinase C (PKC). A family of proteins with at least 12 isoforms that serves as intracellular signaling molecules. They are involved in activating pathways involved in diabetic retinopathy.

proteinase (also, protease). A protein that cleaves another protein, usually at a specific amino acid sequence.

retina. The sensory membrane that lines most of the large posterior chamber of the vertebrate eye. It is composed of several layers including one containing the rods and cones, and functions as the immediate instrument

of vision by receiving the image formed by the lens and converting it into chemical and nervous signals that reach the brain by way of the optic nerve.

retinal ganglion cell. Type of ganglion cell located near the inner surface of the retina. Receives information from the photoreceptor via two intermediate neuron types, the bipolar and amacrine cells.

retinopathy. Any disease or disorder of the retina that can lead to impaired vision or blindness.

retinopathy of prematurity (ROP). An ocular disorder of premature infants occuring when the incompletely vascularized retina undergoes an abnormal pattern of vascularization.

retinal pigment epithelium (RPE). A pigmented cell layer that lies between the choroid and the retina and functions to provide oxygen and nutrients to, and remove waste from, the photoreceptors.

rheology. Study of the deformation and flow of matter.

sea fans. Tufts of neovascularization characterized by profuse fluorescein leakage, which resemble the structure of sea fans in their appearance.

sequelae. Any abnormal condition that occurs subsequent to and/or is caused by disease, injury, or treatment.

serine protease. One of a class of proteins containing a serine residue in its active site that cleaves a peptide bond in another protein.

splenomegaly. Abnormal enlargement of the spleen.

stem cell. An unspecialized cell that gives rise to differentiated cells. strabismus. Inability of one eye to attain binocular vision with the other

because the muscles of the eye are imbalanced.

sympathectomy. Surgical disruption of sympathetic nerve pathways. urokinase plasminogen activator (uPA). A serine protease that cleaves

plasminogen to form plasmin, initiating a proteolytic cascade that leads to, among other things, the degradation of the extracellular matrix.

vascular endothelial growth factor (VEGF). A protein involved in both angiogenesis and vasculogenesis and acting primarily on the vascular endothelium. Its production is upregulated by the presence of hypoxiainducible factor (HIF), a protein responsive to oxygen levels. Retinal ischemia can stimulate the synthesis of VEGF.

vasculogenesis. The de novo development of a blood vessel network through the differentiation of endothelial precursor cells.

vaso-attenuation. Any process by which the growth of vasculature or the extent of existing vasculature is attenuated.

vaso-obliteration. The physical collapse of a blood vessel or blood vessel network.

vitreous humor. The colorless transparent jelly that fills the posterior eyeball, between the retina and the lens.

zymography. An electrophoretic technique, based on SDS-PAGE, that includes a substrate co-polymerised with the polyacrylamide gel for the detection of proteolytic enzyme activity.