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In experimental immunogenic keratitis, provoked in rabbits by intracorneal injection of 20 microliters of human serum albumin (HSA), various anti-inflammatory agents were studied in their effects on corneal edema, neovascularisation and leukocyte infiltration. Prophylactic treatment with a corticosteroid completely prevented the occurrence of keratitis. Nonsteroidal anti-inflammatory drugs such as a cyclooxygenase inhibitor partly prevented neovascularisation and corneal edema, a lipoxygenase inhibitor, a leukotriene antagonist or platelet-activating factor (PAF)-antagonist BN 52021 partially prevented mainly leukocyte infiltration. Prophylactic topical treatment with the poly-unsaturated fatty acids eicosapentaenoic acid and columbinic acid or a dietary supplement with fish oil showed less symptoms of keratitis in all respects.

The inhibitors of prostaglandin (PG) or leukotriene (LT) synthesis and antagonists of platelet-activating factor (PAF) or LTs are inhibitory in experimental keratitis and clinical symptoms of keratitis are reproduced by application of these lipid mediators. This suggests that PGE2, LTB4, LTD4, and PAF are involved in experimental immunogenic and toxic keratitis. The objective of the present study is the measurement of the concentrations of lipid mediators in the aqueous humour and their release by the cornea and iris during keratitis. In both inflammatory models the concentrations of PGE2, LTB4, LTD4, and PAF in the aqueous humour were significantly increased as compared to their controls. The release of PGE2, LTB4 and LTD4 from the cornea, and of PGE2, LTB4, and PAF from the iris was significantly increased compared to that from control tissues. The results are consistent with a role for these lipid mediators in the inflammatory models. Combined therapeutic use of synthesis inhibitors or antagonists of these mediators in eye inflammation seems possible and may serve as an alternative to topical corticosteroid therapy.

Antagonists of leukotriene D4 (LTD4), 3-[7-(2-n-propyl-3-hydroxy-4-acetyl- phenoxy)-propoxy-2-methyl-3,4-dihydro-4-8-n-propyl-2H-1-benzopyran- 2-yl]-propionic acid (SC-39070) and 7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxy- propoxy]-4-methyl- 2-oxo-2H-1-benzopyran-3-acetic acid (FPL-60319) were locally administered to eyes of rabbits with immunogenic keratitis. The period of circular leukocyte infiltration (Wessely's ring) in the cornea was markedly decreased. Edema and neovascularization of the cornea were not influenced.

Fish lipids contain large amounts of eicosapentaenoic acid (EPA) and docosahexaenoic acid. These fatty acids are known to have an influence on prostaglandin (PG) and leukotriene (LT) synthesis. We studied the effect of a fish oil dietary supplement on an immune-complex-induced keratitis of the rabbit eye and compared it with the effect of a sunflower seed oil dietary supplement, rich in linoleic acid. Immune complex keratitis induced by intrastromal injection of human serum albumin (HSA) was characterized by leukocyte infiltrate, neovascularization, and corneal edema. Animals given a fish oil diet showed significantly less leukocyte infiltrate, neovascularization, and corneal edema, compared to those given a sunflower seed oil diet.

In rabbits inflammation of the cornea was induced by intrastromal injection of horse serum. Between 2 and 4 weeks after injection, infiltration of the cornea with leukocytes and neovascularization could be observed. During this period, the rabbits were killed and their corneas analyzed for protein, alkaline phosphatase, acid phosphatase, N-acetyl-beta-D-glucosaminidase, and lactate dehydrogenase. The enzyme activities in the inflamed corneal stroma reflect the high lysosomal activity, which probably originates from the leukocytes. The enzyme activities in the epithelium indicate that the tissue is abnormal and undergoing repair processes.

Intrastromal injection with human serum albumin (HSA) in the rabbit cornea induced edema and a ring-shaped leukocyte infiltrate followed by neovascularization. The effect of topically administered lipoxygenase and cyclooxygenase inhibitors on this inflammatory keratitis was studied. The lipoxygenase inhibitors Bay 08276 and Rev 5901 and the cyclooxygenase inhibitor suprofen were given as 1% eye drops three times daily during the experiment. In eyes treated with lipoxygenase inhibitors leukocyte infiltration, neovascularization and edema formation decreased. In eyes treated with a cyclooxygenase inhibitor the period of neovascularization was slightly shortened and corneal edema decreased. No influence on leukocyte infiltration was seen.

The effect of topically administrated indomethacin was studied in rabbits on an experimentally provoked inflammatory keratitis. Intrastromal injection with horse serum induced in the cornea a ring-shaped infiltration with leukocytes and neovascularization. Indomethacin was given as eye drops three times daily during the experiment. In the indomethacin treated eyes leukocyte infiltration was prolonged but not the concomitant neovascularization. The potentiation of the leukocyte response may be due to a facilitation of chemotactic lipoxygenase products.

Low doses of indomethacin were applied topically to rabbit eyes in an experimental model of immunologically provoked inflammatory keratitis. Leucocyte infiltration was potentiated but not the concomitant neovascularization.

Several unsaturated fatty acids are precursors of prostaglandins and leukotrienes. Depending on their precursor, these prostaglandins and leukotrienes have different biological characteristics. The effects of topically administered fatty acids on an experimentally provoked inflammatory keratitis were studied in rabbits. Intrastromal injection with human serum albumin induced in the cornea a ring-shaped infiltration with leukocytes, corneal edema and neovascularization. Arachidonic, gamma-linolenic, dihomo-gamma-linolenic (DHGL), eicosapentaenoic (EPA) and columbinic acid were given as eye drops in a suspension in hydroxypropylmethylcellulose 0.5% three times daily during the experiment. EPA, DHGL, columbinic, and gamma-linolenic, but not arachidonic acid, showed a significant inhibition of either leukocyte infiltration, edema or neovascularization. The inhibitory effects of these fatty acids may be caused by topical inhibition of the formation of prostaglandins and leukotrienes in the arachidonic acid cascade in the rabbit cornea.

Topical administration of prostaglandin E1 (PGE1) and prostaglandin F2 alpha (PGF2 alpha) prior to ocular trauma can reduce the ocular inflammatory response in rabbits. In the present study, the ocular trauma consisted of puncture of the cornea, without aspiration of aqueous. Corneal puncture, which causes and inflammatory response, a breakdown of the blood-aqueous barrier, and a biphasic response of the intraocular pressure (IOP), yields a valid model of a mild inflammatory response. Pretreatment with PGE1 and PGF2 alpha led to a lower rise in the aqueous prostaglandin E2 (PGE2) concentration and a reduced inflammatory response after corneal puncture; in addition, the increase in the aqueous protein concentration was smaller and the aqueous ascorbate level was higher. The lower increase in the aqueous PGE2 concentration after pretreatment with PGs correlated with the reduced changes in IOP. It is suggested that PGE1 and PGF2 alpha reduced the trauma-induced inflammatory response by decreasing the formation of endogenous prostaglandins, as reflected by their concentration in aqueous. This study also indicates that the results of studies that require perforation of the cornea or cannulation of the anterior chamber may be affected by profound changes in the levels of cyclo-oxygenase products in the tissues surrounding the aqueous.