dinoprost and Uveitis

Two prostaglandin molecules have important physiological and pathophysiological role in the tissues of the eye. Prostaglandin F2 alpha takes part in mediating intraocular pressure, prostaglandin E2 is the mediator of inflammation. In case of increased intraocular pressure, latanoprost a derivative of prostaglandin F2 alpha can be applied. Numerous data are available on the favourable intraocular pressure lowering effect of latanoprost. It can be applied as a single hypotensive or it can be combined with eye-drops currently used in glaucoma. It exerts its therapeutic effect by increasing uveoscleral outflow. Inflammation in the eye can be diminished by nonsteroidal anti-inflammatory drugs similarly to inflammations in other tissues of the organism. Literature on nonsteroidal anti-inflammatory drugs is enormous. Molecules of different structures inhibit the synthesis of prostaglandins. Primarily they are useful anti-inflammatory agents, reduce intraocular pressure in secundary glaucoma, inhibit intraocular miosis and prevent development of cystoid macula oedema. Nonsteroidal anti-inflammatory drugs do not exert their effects on prostaglandins themselves, but inhibit their synthesis. Hence the use of both, latanoprost and nonsteroidal anti-inflammatory drugs simultaneously, improves safety of therapy in case of patients prone to uveitis.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Dinoprost; Dinoprostone; Eye; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ocular Physiological Phenomena; Prostaglandins; Prostaglandins F, Synthetic; Uveitis

Uveitis is a prevalent intraocular inflammatory disease and one of the most damaging ocular conditions. Pretreatment with melatonin prevented ocular inflammation induced by an intravitreal injection of bacterial LPS in the Syrian hamster. Here, we have assessed the anti-inflammatory effects of melatonin administered after the onset of ocular inflammation.. The eyes of male Syrian hamsters were intravitreally injected with vehicle or LPS. Melatonin was injected i.p. every 24 h, starting 12 or 24 h after the LPS injection. A clinical evaluation (with a score index based on clinical symptoms), the number of infiltrating cells, protein concentration and PGE2 and PGF2α levels in the aqueous humour, as well as retinal NOS activity, lipid peroxidation and TNF-α levels were assessed. Retinal function was assessed by scotopic electroretinography, and light microscopy and immunohistochemistry were used to evaluate the state of the retinal structure.. Both treatment regimens with melatonin decreased clinical symptoms, reduced the leakage of cells and proteins, and decreased PG levels in aqueous humour from eyes injected with LPS. In addition, melatonin treatment blocked the decrease in scotopic electroretinogram a- and b-wave amplitude, protected the retinal structure and reduced the increase in NOS activity, lipid peroxidation and TNF-α levels, induced by LPS.. These results indicate that treatment with melatonin, starting after the onset of uveitis, attenuated ocular inflammation induced by LPS in the Syrian hamster and support the use of melatonin as a therapeutic resource for uveitis treatment.

Topics: Animals; Antioxidants; Aqueous Humor; Cricetinae; Dinoprost; Dinoprostone; Disease Models, Animal; Electroretinography; Immunohistochemistry; Intravitreal Injections; Lipid Peroxidation; Lipopolysaccharides; Male; Melatonin; Mesocricetus; Nitric Oxide Synthase; Retina; Tumor Necrosis Factor-alpha; Uveitis

We examined the effects of prostaglandin analogues on the blood-aqueous barrier(BAB) permeability in rabbit eyes at an early phase of endotoxin-induced uveitis(EIU).. One drop of 0.005% latanoprost or 0.12% unoprostone were applied to rabbit eyes. Escherichia coli lipopolysaccharides were injected to induce uveitis. The changes in flare intensity in normal eyes and EIU eyes after application of eye drops were evaluated. The effect of cyclooxygenase inhibitor on the flare intensity changes caused by the application of unoprostone was also examined.. Flare intensity increased significantly after a single instillation of unoprostone, and the increase was not prevented by pretreatment with cyclooxygenase inhibitor. In eyes with EIU, unoprostone caused an additional increase of flare intensity to uveitis induced flare change. Latanoprost had no effects on BAB in eyes with normal and with uveitic conditions.. Latanoprost and unoprostone did not cause an excessive inflammatory reaction in rabbit eyes at an early phase of EIU.

Topics: Animals; Blood-Aqueous Barrier; Dinoprost; Female; Latanoprost; Male; Prostaglandins F, Synthetic; Rabbits; Uveitis

In the preinflammatory phase of S-antigen (S-ag) induced uveitis, an ocular hypotension occurs between day 2 and day 6 after S-ag injection. To better understand this phenomenon, we studied the levels of prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) in the aqueous humor of S-ag injected rats at various time points after induction of disease.. Twenty-five female Lewis rats weighting 150 to 175 gm were injected in the hind foot-pad with 50 micrograms of S-antigen. IOP was measured each day at 9 am with a Tono-Pen tonometer. Aqueous humor was collected at days 0, 2, 4, 6, 9, 14 and 18 after S-ag injection. PGE2 and PGF2-alpha were assayed in the aqueous humor using an enzyme immunoassay method.. The concentration of PGE2 increased after day 6 and peaked at day 14 after S-ag injection (45.6 +/- 9.0 mu/ml vs 1.1 +/- 0.1 mu/ml in controls, P = 0.04). The peak of PGE2 corresponded to the maximum inflammation and ocular hypertension. PGF2-alpha was increased from day 2 to day 6, with a peak at day 6 after S-ag injection (128.0 +/- 51 pg/ml vs 56 +/- 2.0 pg/ml in controls, P = 0.047), which corresponded to the preinflammatory ocular hypotension. A second peak was observed at day 18 after S-ag injection (3643 +/- 824 pg/ml, P = 0.049), which corresponded to the cessation of intraocular inflammation and ocular hypertension.. The early increased concentration of PGF2-alpha in the aqueous humor of rats with S-ag induced uveitis may explain the ocular hypotension observed from day 2 to day 6 after S-ag injection.

Topics: Animals; Aqueous Humor; Dinoprost; Dinoprostone; Female; Glaucoma; Intraocular Pressure; Rats; Rats, Inbred Lew; Uveitis

Intraocular inflammation was induced in the rat by footpad injection of salmonella endotoxin in order to study the influence of chemical inflammation mediators in this uveitis model. Ocular inflammation was assessed 1, 6, 18, 24 and 72 h after endotoxin administration as well as in control rats, by measuring aqueous protein concentration, aqueous inflammatory cell content, and pupillary diameter. Thromboxane B2 (TXB2), prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2-alpha), leukotriene B4 (LTB4), and substance P were simultaneously measured in the aqueous humor by radioimmunoassay. Inflammation parameters peaked at 18 h. TXB2 was already significantly elevated at 1 h. PGE2 peak values of 2.7 ng/ml were reached at 18 h. PGF2-alpha was never significantly raised over control values. LTB4 peaked at 18 h, together with a polymorphonuclear peak. Substance P was significantly elevated after 6 h. It is concluded that maximal uveitis in this model occurs at 18 h. TXB2 is an early mediator, and PGE2 is probably implicated in blood-ocular barrier disruption for which levels as high as 2.7 ng/ml in aqueous seem necessary. PGF2-alpha does not play a major role in this model, while LTB4 seems to be the main chemotactic factor for polymorphonuclears (PMNs) in the anterior chamber and substance P is clearly related to pupil miosis.

Topics: Animals; Aqueous Humor; Dinoprost; Dinoprostone; Endotoxins; Leukotriene B4; Male; Pupil; Rats; Rats, Inbred Lew; Salmonella; Substance P; Thromboxane B2; Uveitis

We have assessed the efficacy of 0.5% piroxicam collyrium applied for 15 days to the eyes of rabbits in which uveitis had been experimentally induced. The results demonstrate the capability of the drug to easily overcome the ocular barrier. On the 30th day, a clear regression of the uveitis symptoms was observed, the hyperaemia having completely disappeared. By means of radioimmunological assay (RIA), it was found that the increased PGF2 alpha concentration in the aqueous humour had returned to normal levels.

Topics: Administration, Topical; Animals; Dinoprost; Male; Piroxicam; Prostaglandins F; Rabbits; Radioimmunoassay; Uveitis