Abstract

The pathology of intraocular neovascularization was studied in human and animal eyes by means of electron microscopy and histochemistry, and also by tissue culture of bovine retinal small vessels. The newly formed vessels in the vitreous obtained at the time of vitrectomy from the eyes with proliferative diabetic retinopathy and retinal vein occlusion lacked tight junction and formed fenestration in the endothelial cells. When 1 microgram of the basic fibroblast growth factor (b-FGF) enveloped in ethylene vinyl acetate copolymer was implanted into the vitreous of monkey eyes, new vessels were formed in the iris in all eyes and in the vitreous in 12 eyes out of 14 experimental eyes. The origins of new vessels were the iris vessels in the iris, and both stromal vessels of the ciliary body and retinal vessels in the vitreous. These vessels showed fenestration in the endothelial cells. The activity of the lysosomal enzyme detected by acid phosphatase increased in the epithelial layer of the ciliary body. The new vessels in the vitreous of rabbits were seen in 9 out of 10 eyes when b-FGF was implanted in the vitreous with an intravitreal injection of amino adipic acid solution (1 mg in 0.2 ml of physical saline), although none of the 8 eyes formed new vessels when sodium iodate was injected intravenously after implantation of b-FGF with aminoadipic acid. Corneal neovascularization was formed by implantation of 250 ng of b-FGF into the corneal micropockets of the guinea pigs, and regressed after the b-FGF was removed. The endothelial budding and protrusion were frequently seen during the course of neovascularization. Immunohistochemical detections showed positive stainings for fibronectin in most front-end lesions, for laminin and type 4 collagen associated with the endothelial cells, and for factor VIII only on the endothelial cells which formed the vascular lumen. The acid phosphatase activity was detected on the leucocytes infiltrating in the corneal stroma. In the course of regression of corneal neovascularization, initial pathological change was thrombus formation followed by disappearance of endothelial cells, although the basement membrane of the endothelial cells remained. Fibronectin reduced its activity in the early stage of regression, laminin and type 4 collagen remained even after the vascular lumen had subsided, and factor VIII was stained in a geographically irregular manner. Migrating activity of the cultured-bovine retinal small vessels was accelerated by fibronectin and fetal bovine serum.