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Site-directed neovessel formation in vivo.

Angiogenesis is an important component of organogenesis and wound repair and occurs during the pathology of oncogenesis, atherogenesis, and other disease processes. Thus, it is important to understand the physiological mechanisms that control neovascularization, especially with methods that permit the molecular dissection of the phenomenon in vivo. Heparin-binding growth factor-1 was shown to bind to collagen type I and type IV. When complexed with gelatin, heparin-binding growth factor-1 can induce neovascularization at polypeptide concentrations that are consistent with the biological activity of the mitogen in vitro. The adsorption strategy induces rapid blood vessel formation at and between organ- and tissue-specific sites and permits recovery of the site-specific implant for examination and manipulation by molecular methods.

Animals

Senile disciform macular degeneration complicated by massive hemorrhagic retinal detachment and angle closure glaucoma.

Six eyes developed angle-closure glaucoma secondary to total hemorrhagic retinal detachment that occurred as a rare complication of senile disciform macular degeneration. The patients were all elderly with known senile macular choroidal degeneration. They had no history of eye surgery and experienced sudden loss of vision followed by pain. Balloons of retinal detachment were pushed tightly against the lens in a characteristic "Y suture" appearance causing shallowing of the anterior chamber and glaucoma. Pathologic examination of three eyes revealed that the choroid was not detached but that a massive subretinal hemorrhage was present. Neovascular tissue in macular disciform lesions was found in every case and was the probable source of hemorrhage. Sheets of avulsed retinal outer segments were seen incarcerated in subretinal blood in two cases, and drainage of this subretinal blood in three cases did not restore useful vision.

Aged

Mast cell interactions with the nervous system: relationship to mechanisms of disease.

In summary, mast cell interactions in the nervous system are relevant to both physiological processes (i.e. reproduction) and pathologic states (i.e. inflammatory demyelination, painful disorders, toxic and metabolic disease, and tumor angiogenesis). Their physiologic roles may contribute to gender-related vulnerability to inflammatory disease and may modulate sensitivity to pain. Mast cells are universally involved in tissue repair and they release and respond to trophic factors such as NGF. These cells also produce and react to cytokines, and thus appear to play a role in tissue degeneration as well as repair. In certain neurological diseases, i.e. multiple sclerosis and Guillain-Barré syndrome, the ability of mast cell proteases to degrade specific myelin proteins suggests that these cells are agents, rather than bystanders, in the demyelinative process. Even more intriguing is their recently identified capacity to process bacterial antigen as efficiently as activated macrophages, suggesting that a more critical role than previously suspected might be considered for mast cells in CNS and PNS demyelination. In experimental metabolic disorders such as galactose intoxication and thiamine deficiency, mast cells appear to play a pathogenic role. Thus, in galactose intoxication, altered BNB vascular permeability occurs in conjunction with mast cell proliferation and degranulation, while in thiamine deficiency, increased histamine levels have been reported in the rat thalamus (79) and are associated with cell death and proliferation as well as mast cell degranulation (Powell and Langlais, unpublished observations). Structural interactions between mast cells and a variety of other cells have been observed, as well as close approximation of mast cells to nerve endings in tissues in which mast cells are especially active. Due to their paracrine nature, mast cells can modulate events in their microenvironment through explosive degranulation, piecemeal degranulation, or "transgranulation" as they insert granules into neighboring cells. Lastly, these cells play specific roles in reparative processes, e.g. angiogenesis, and are active in neoplastic states, including von Recklinghausen's disease (neurofibromatosis). Their involvement may have been underestimated in neuropathological studies, to date, by a reliance on staining techniques that are inadequate for identifying degranulated and therefore activated mast cells (4). More exacting histochemical and immunostaining procedures will help to fully realize the extent of their participation in physiological and pathological processes.

Animals

Subfoveal choroidal neovascularization in punctate inner choroidopathy. Surgical management and pathologic findings.

PURPOSES: To evaluate submacular surgery for the management of subfoveal choroidal neovascularization in punctate inner choroidopathy, to describe the histopathology and ultrastructure of the excised subretinal tissue, and to propose a staging system that characterizes the development of choroidal neovascularization with associated subretinal fibrosis. METHODS: The authors reviewed the records of five patients (6 eyes) with punctate inner choroidopathy who underwent submacular surgery for subfoveal choroidal neovascularization. Surgical specimens were examined using light and transmission electron microscopy. RESULTS: Visual improvement was noted postoperatively in all six eyes, with follow-up ranging from 8 to 36 months (median, 14 months). Recurrences (6 in 4 eyes) were common. Five of the six recurrences required additional procedures: three were managed surgically, two with laser photocoagulation, and one with observation. "Bridging" of separate foci of choroidal neovascularization resulted in stellate or "dumbbell-shaped" areas of subretinal fibrosis in four of six eyes. Histopathologic evaluation of the excised tissue showed endothelial-lined vascular channels, retinal pigment epithelium, lymphocytes, plasma cells, fibrocytes, collagen fragments, and rarely, outer retinal elements. CONCLUSIONS: Subfoveal choroidal neovascularization in punctate inner choroidopathy may be managed with submacular surgery. Recurrences are common and may result in substantial loss of vision. Choroidal neovascular membranes with an accompanying fibrotic reaction are responsible for the stellate or dumbbell-shaped areas of subretinal fibrosis. No beneficial effect was demonstrated using corticosteroid treatment of the choroidal neovascularization.

Adult

Argon laser panretinal photocoagulation in ischemic central retinal vein occlusion. A 10-year prospective study.

We conducted a prospective, planned study of argon laser panretinal photocoagulation (PRP) in ischemic central retinal vein occlusion (CRVO) over a 10-year period in 123 eyes. On comparing the lasered eyes versus the nonlasered eyes, there was no statistically significant difference between the two groups in the incidence of development of angle neovascularization (NV), neovascular glaucoma (NVG), retinal and/or optic disc NV, or vitreous hemorrhage, or in visual acuity. Our study, however, did show a statistically significant (P = 0.04) difference in the incidence of iris NV between the two groups, with iris NV less prevalent in the laser group than in the nonlaser group, but only when the PRP was performed within 90 days after the onset of CRVO. The other parameter which showed a statistically significant difference between the two groups was the peripheral visual fields-the laser group suffered a significantly (P less than or equal to 0.03) greater loss than the non-laser group. We discuss the implications of these findings in light of the natural history of ischemic CRVO and of ocular NV. Since the original rationale for advocating PRP in ischemic CRVO was the proven beneficial effect of PRP on ocular NV in proliferative diabetic retinopathy, we also discuss the disparities in the disease process between ischemic CRVO and proliferative diabetic retinopathy and in their responses to PRP.

Aged

Heparan structure and the modulation of angiogenesis.

It is postulated that the angiogenic potential of tissues is influenced by the fine structure of heparan glycosaminoglycans present in the tissues. Possible mechanisms involved are discussed. It is suggested that compounds chemically related to heparans might usefully act as inhibitors of pathological angiogenesis.

Capillaries

[Biomorphosis of arteries].

The discrimination between normal aging and disease is very difficult, especially in the vascular system. The main factors, gene expression, physical forces, and environmental conditions are effective in normal and pathological circumstances. The changes in extracellular and cellular level are described. During aging, a fibrosis and a reduction of the cellular functions in the vascular wall are found. This deteriorates the blood streaming and favours pathological processes, e.g. atherosclerosis.

Aging

Radiation choroidopathy with remodeling of the choroidal venous system.

PURPOSE: To describe a case of radiation choroidopathy manifesting drastic remodeling of choroidal drainage routes. METHOD: Case report. A 34-year-old man who had received radiation treatment for a tumor in the upper eyelid of his right eye 15 years earlier had floating black spots. He was examined ophthalmologically, including with indocyanine green angiography using a scanning laser ophthalmoscope. RESULTS: The right eye manifested classic features of radiation retinopathy in the superior fundus. Indocyanine green angiography showed vaso-occlusion of choroidal arteries, capillaries, and veins in a wider area than that affected by radiation retinopathy. The superotemporal vortex vein was obliterated, resulting in a remodeling of the choroidal veins in the same quadrant. The blood in this quadrant drained into the inferotemporal vortex vein through collateral venovenous drainage routes. CONCLUSION: The diagnosis in this eye was radiation retinopathy and radiation choroidopathy. Choroidal vascular lesions were more pronounced and involved a wider area than retinal vascular lesions did. This case illustrates that the choroidal veins may manifest a vast plasticity to remodel the drainage route after obliteration of a major vortex vein.

Adult

Oxygenation and vasodilatation in relation to diabetic and other proliferative retinopathies.

The features of proliferative retinopathies are reviewed with reference to the vasodilatation that is a common stage in their pathogenesis. Vasodilatation in the retina is discussed in terms of a model in which vessel wall stretch in the retinal venules leads to leakage and proliferation. The beneficial effects of treatments such as panretinal photocoagulation and vitrectomy on the retinal hemodynamics are shown to agree with the hypothetical model.

Animals

Angiogenic growth factors.

Angiogenesis, the formation of new blood vessels, plays a central role in a variety of physiological and pathological processes such as embryonic development, wound healing and tumor growth. It is a complex, multi-step process that involves the migration and proliferation of capillary endothelial cells. Several factors that stimulate the proliferation of endothelial cells in vitro have been shown to induce angiogenesis in vivo. Among these angiogenic growth factors are wide-spectrum multifunctional mitogens (e.g. the fibroblast growth factors) and the recently identified factors with distinct specificity for vascular endothelial cells (e.g. the platelet-derived endothelial cell growth factor). Another group of factors apparently induce angiogenesis indirectly (e.g. transforming growth factor-beta) by stimulating target cells to release angiogenic factors or by other mechanisms. The differential expression, release and activation of these factors might regulate angiogenesis under various physiological and pathological conditions.

Angiogenesis Inducing Agents

[Diabetic choroidopathy--a retrospective fluorescein angiography study. Preliminary report].

Both histologic studies and findings with Indocyanin green angiography furnish clear indications of the existence of diabetic choroidopathy. Out of 19,387 fluorescein angiograms made over the last 15 years at the First Ophthalmological Clinic of Vienna University, 902 were selected in which the choroidal vascular system is at least partially visible due to melanin hypopigmentation. The pathologic changes in the choroid observed in these angiograms can be allocated in two basic types of pathologic fluorescence: on the one hand hyperfluorescent lesions such as drusen in Bruch's membrane in suprisingly young diabetics, extremely hyperfluorescent lobules of the choriocapillaris, choroidal aneurysms, and neovascularizations; on the other hand, hypofluorescent lesions or structures were observed, such as delayed filling of the choriocapillaris and, in the late phase of angiography, varicose and tortuous choroidal vessels, drained and appearing dark in contrast to the diffuse background fluorescence.

Aneurysm

Factors controlling ocular angiogenesis.

PURPOSE: To provide an overview of the cellular and molecular factors involved in ocular angiogenesis. METHODS: A literature search and review encompassing a broad range of medical and basic science disciplines was undertaken to survey contemporary insights into the mechanisms of angiogenic stimulation and inhibition. RESULTS: Ocular angiogenesis is a complex pathophysiologic process. Factors have been isolated that play key roles in the regulation of angiogenesis. The influence of stimulating growth factors is counterbalanced by a number of antiproliferative agents. The net result of these opposing factors on the vascular endothelial cell determines the outcome of angiogenesis homeostasis. Both endogenous and synthetic molecules can regulate ocular angiogenesis. CONCLUSIONS: The isolation and synthesis of molecular regulators of angiogenesis has enhanced our understanding of this process. Clinical trials are underway to determine the efficacy of these agents in controlling pathologic angiogenesis, including that in ocular disease.

Endothelium, Vascular