Quantitation of acute experimental ocular inflammation with 111indium-leukocytes.

The cellular component of an acute ocular inflammation in rabbits was measured with autologous leukocytes exogenously labeled with 111Indium tropolonate. Inflammation was induced by intravitreal bacterial lipopolysaccharide (LPS). After 16 hr blood was removed, leukocytes separated, labeled with 111Indium tropolonate and reinjected. Three cell fractions were examined: a leukocyte rich fraction which had been prepared with Dextran; and polymorphonuclear and mononuclear leukocyte fractions which had been prepared using a discontinuous Percoll gradient. Two hours after labeled leukocytes were injected, measurements of 111Indium were made in blood, plasma, the whole eye and in ocular compartments. From these data the numbers of each leukocyte population present were estimated and compared directly to histopathologic changes. Both polymorphonuclear and mononuclear leukocytes entered ocular tissues during the 2 hr period beginning 20 hr after LPS injection. Altered ocular vascular permeability was successfully measured with 125Iodine-albumin in some of these same rabbits. Both the number and type of inflammatory cell entering ocular tissues during a set period of time of the inflammatory response could thus be measured. This technique provides an opportunity to define the relationship of leukocyte infiltration and altered ocular vascular permeability in ocular tissues during the inflammatory response.

Mononuclear cells in the corneal response to endotoxin.

A severe keratitis can be produced after the direct injection of bacterial endotoxin, or lipopolysaccharide (LPS), in rabbits. Corneal inflammation can progress to scarring and vascularization within a 2 to 3 week period. Pretreatment with systemic adrenal corticosteroids (triamcinolone) prevents this response. Limbal cellular and vascular events were studied during the first 20 hr after injection of LPS in treated and nontreated rabbits. Perivascular limbal inflammatory cells were counted and limbal vascular permeability was assessed by extravasation of 131I-albumin and 125I-fibrinogen in the cornea. Corticosteroids decreased but did not prevent the early protein extravasation and profoundly altered the inflammatory cell population around blood vessels at the limbus. Mononuclear cells, particularly mononuclear phagocytes, were sharply reduced. It is proposed that these cell types play an important role in the perpetuation and amplification of the inflammatory response in this reaction.

Cellular and vascular responses in acute experimental ocular inflammation.

PURPOSE: To measure simultaneously blood volume, altered vascular permeability, and leukocyte extravasation in ocular inflammation in rabbits at various times and in different anatomic locations after intravitreal endotoxin (lipopolysaccharide [LPS]). METHODS: Nuclides of different emission and decay were used for labeling and then injected intravenously. Ocular blood volumes were measured with technetium 99m, altered vascular permeability with I-125 albumin, and polymorphonuclear leukocyte or mononuclear cell extravasation after labeling with Indium 111. Eyes were divided into anterior eye section, iris-ciliary body, aqueous, and vitreous and posterior eye sections, and measurements were made at 3, 6, 9, 18, and 24 hours after intravitreal LPS injection. Blood volume measurements made it possible to estimate the amount of extravascular protein and the number of extravascular leukocytes. RESULTS: Blood volumes were consistently elevated at all times, usually by approximately 50% and predominantly in the anterior segment. Altered vascular permeability was present at 3 hours, increased at 6 hours, decreased at 9 hours, and was elevated at 18 to 24 hours, predominantly in the anterior eye. Leukocytes in iris-ciliary body appeared in small numbers at 6 hours, increased at 9 hours, and continued to extravasate at 18 and 24 hours. Mononuclear cells were as numerous as polymorphonuclear leukocytes at each time measured. CONCLUSIONS: The quantitation of multiple parameters of ocular inflammation in this experimental model has been helpful in defining when and in what tissue changes occur. Leukocytes are primarily within tissues, particularly in the iris-ciliary body region. Mononuclear leukocytes are a prominent feature at all times and add further support to the concept that the mononuclear phagocyte plays a pivotal role in reactions to LPS.

The structural basis of altered vascular permeability following intraocular inflammation.

An immunogenic uveitis was produced in rabbits by the intravitreal injection of bovine gamma-globulin. Four to six months later, an alteration in vascular permeability was determined by greater accumulation of iodinated I 125 serum albumin in the previously inflamed eye than in the normal eye. An altered vascular permeability was found only in eyes with profound structural changes. Possible sites of extravascular protein leakage were: (1) proliferated blood vessels in the posterior chamber and vitreous; and (2) leakage through the disrupted and scarred ciliary epithelium. In eyes without evidence of altered vascular permeability, a persistent chronic inflammation was observed, and gliosis and chorioretinal scarring was prominent.