Experimental immunogenic rubeosis iridis.

We have developed a primate model of rubeosis iridis in monkeys systemically sensitized to crystalline beef insulin. After intravitreal insulin injection, the dose-related immunogenic inflammation includes cells, flare, fibrin, and blood in the anterior chamber. With more severe inflammation, posterior synechiae, iris bombé, and cataracts occur. Of particular importance, new blood vessels develop within the stroma and on the anterior surface of the iris. Following injection of small amounts of insulin, the anterior surface vessels may regress over time, and the iris regains its normal appearance and coloration. However, the new stromal vessels persist and are cuffed by inflammatory cells including plasma cells. After injection of large amounts of insulin, more extensive structural alterations develop as noted above in conjunction with persistent iris anterior surface and stromal neovascularization. The relationship of rubeosis iridis to clinical inflammatory syndromes and to previous laboratory studies is discussed. Stromal neovascularization was a consistent finding in this experimental model even when anterior surface vessels regressed. On the basis of these experimental data and a review of publications describing human pathology, we believe that a broadening of the classic definition of rubeosis iridis is waranted to include a recognition of the stromal component of the clinical and pathologic findings.

Experimental immunogenic proliferative retinopathy in monkeys.

When a small amount of bovine serum albumin (BSA) was injected into the posterior vitreous body of a sensitized monkey, an immunogenic response occurred in the major blood vessels of the optic disk. In nonsensitized monkeys, the same phenomenon appeared after repeated intravitreal injections of small amounts of BSA. Focal leaks of fluorescein from the optic disk vessels were demonstrated by fluorescein angiography. Correlative light and electron microscopy revealed infiltration of acute and chronic inflammatory cells from the vessels of the optic disk into the vitreous body. When larger amounts of BSA were injected in sensitized monkeys, in addition to optic nerve involvement, there were scattered retinal vascular hemorrhagic and exudative lesions throughout the posterior pole. Immunologic mechanisms can result in preferential optic disk involvement with formation of proliferative lesions during the healing phase of the immunogenic inflammation.

Structural alterations in the ciliary process and the blood-aqueous barrier of the monkey after systemic urea injections.

The structural alterations induced in the monkey ciliary epithelium by intravascular injection of urea solutions were studied with the light and electron microscopes. Arterial injection of urea resulted in destruction of the nonpigmented epithelium and the consequent breakdown of the blood-aqueous barrier. The intravenous injection did not significantly affect the structural integrity of the ciliary epithelium. The intercellular zonulae occludens were not altered and the intercellular pathway from blood to posterior chamber remained closed to horseradish peroxidase. Intercellular uptake in large cytoplasmic vacuoles appeared to account for some late transport to the basal end of the nonpigmented epithelium. There was no comparable transport of peroxidase in vesicles or vacuoles through the nonpigmented epithelium in animals not subjected to intravenous urea treatment. Compared to the arterial route, intravenous administration of urea does not appear to pose a serious threat to the integrity of the ciliary epithelium.

Rubeosis iridis generated by insulin hypersensitivity.

There are important similarities between human and experimental monkey rubeosis iridis. We believe that we have developed a useful primate model to study iris neovascularization and that the possible role of immunity to insulin in the pathogenesis of human diabetic rubeosis iridis warrants further detailed consideration.

Effect of prostaglandin on the blood aqueous barrier in the rabbit ciliary process.

Distinct structural changes occur in the rabbit ciliary epithelium following intravitreal injection of prostaglandin E-1 (PGE-1). Up to four hours after PGE-1 administration, alteration of the pigmented epithelium was characterized by dilated intercellular spaces and the disruption of many intercellular junctions. The nonpigmented epithelium demonstrates a spectrum of morphologic variation from only some thinning of cytoplasmic processes to area of severe distortion. In these regions, marked thinning of the nonpigmented cells occurs in association with an absence of apical tight junctions. This alteration of the nonpigmented epithelium and its tight junctions allows for the leakage of proteins into the posterior chamber which is consistent with the breakdown in the blood-aqueous barrier. The temporal sequence of these changes would suggest a differential susceptibility of the pigmented and nonpigmented layers with the pigmented layers being affected earliest and the nonpigmented epithelium altered subsequently. The recovery of this epithelial change was rapid and complete and demonstrated the transient effects of PG on the ciliary epithelium with recovery of the blood-aqueous function by 8 hours after injection.

Immunoperoxidase localization of herpes zoster virus and simian virus 40 in cell culture.

The immunoperoxidase technique was used in an electron microscopy study to localize the virions of herpes zoster virus and simian virus 40 in cell cultures. Intranuclear and intracytoplasmic virions of herpes zoster virus were easily and specifically identified due to intense staining by the finely granular, black reaction product. With simian virus 40, intranuclear virions were not stained, whereas intracytoplasmic particles appeared densely black. There was essentially no background staining. Advantages of this technique over the ferritin-labeled antibody method include simpler preparative procedures for reagents, greater penetrability of the antibody conjugate, and internal amplification which substantially improves the ability to localize sites of antigen-antibody reaction. We believe that the immunoperoxidase method can be successfully applied to a wide variety of problems involving viral antigens.