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Experimental autoimmune uveitis (EAU) is a well-known animal model of posterior uveitis that is one of the major causes of blindness. EAU could be induced in susceptible animals (i.e., Lewis rat) by immune reactions using evolutionarily conserved retinal proteins, such as interphoto-receptor retinoid binding protein (IRBP), or epitaphs of the protein. First, we prepared the following four test groups that subsequently increased or decreased inflammation. (1) Normal control group, (2) IRBP-induced uveitis group, (3) Hemin-treated uveitis group, and (4) Sn(IV) protoporphyrin IX dichloride (SnPP)-treated uveitis group. Second, in the vitreous bodies of Lewis rats, the infiltrated proteins were analyzed using two-dimensional electrophoresis (2-DE), MALDI-TOF/MS, and Micro LC/LC-MS/MS analysis. Finally, Western blotting was applied to confirm the relative amount of crystallins and phosphorylation sites of alphaB-crystallin. Thirty spots were identified in vitreous bodies, and 27 of these spots were members of the crystallin family. Unlike betaA4- and B2-crystallins (that were significantly increased without truncation), alphaA- and B-crystallins were only truncated in EAU vitreous body. Taken as a whole, in the rat EAU model, we suggest that post-translational truncations of alphaA- and alphaB-crystallins, phosphorylation of alphaB-crystallin, and new production of betaA4- and betaB2-crystallins are intercorrelated with uveitis progression and inflammatory responses.

Endotoxin-induced uveitis (EIU) is an animal model of acute ocular inflammation. To characterize the mechanism of EIU, we analyzed the infiltration of proteins in the vitreous bodies of rats with EIU and normal rats using 2-DE and micro LC/LC-MS/MS. Twenty spots were identified in vitreous bodies of rats. Eighteen of these spots were members of the crystallin family. The truncated form of beta A4- and beta B2-crystallin were predominant in normal vitreous bodies, but there were intact form of crystallins in lipopolysaccharide-injected rats with EIU. These results suggest that crystallin family proteins are the major group of proteins involved in uveitic vitreous and that C-terminal truncation of beta-crystallins may play a role in EIU-related disease progression.

Various N,N′-disubstituted ureas5 were easily prepared from the corresponding primary amide1 by tratment with N-Bromophthalimide (NBP)-AgOAc-RNH2 4 in dry N,N-dimrthylformamide (DMF). This reaction envolved the intermediate formation of isocyanate3 from amide1 via Hofmann rearrangement by treatment with AgOAc and NBP and nucleophilic addition of amine4 to this isocyante3. This method is simple enough to be applied to the synthesis of various N,N′-disubstututed ureas in large scale conviently.

By using N-bromophthalimide (NBP) as halonium ion source for the Hofmann rearrangement, a series of primary amide could be converted to the corresponding carbamate in excellent yields. So NBP was thought to be very effective and practical halonium ion source for the Hofmann rearrangement.

Purpose: To compare surgical results of two patient groups with punctal obstruction. One group underwent punctoplasty while the other group underwent silicone tube intubation. Methods: We compared postoperatively 48 eyes of 37 patients with punctal obstruction within and after one year of the procedure. 24 eyes of 17 patients had punctoplasty and 24 eyes of 20 patients had silicone tube intubation by the same surgeon. Results: Upon follow-up within one year after the punctoplasty, 13 eyes (54%) showed no epiphora, nine eyes (38%) showed intermittent epiphora, and two eyes (8%) showed persistent epiphora. However, after silicone tube intubation, 20 eyes (83%) showed no epiphora, three eyes (13%) showed intermittent epiphora, and one eye (4%) showed persistent epiphora. Over one year after the punctoplasty, one eye (4%) showed no epiphora, 19 eyes (78%) showed intermittent epiphora, and four eyes (17%) showed persistent epiphora. However, after the silicone tube intubation, 17 eyes (71%) showed no epiphora, six eyes (25%) showed intermittent epiphora, and one eye (4%) showed persistent epiphora. Conclusions: Silicone tube intubation is more effective than punctoplasty in the long term treatment of punctal obstruction.

Experimental autoimmune uveoretinitis (EAU) is a prototypic T-cell-mediated autoimmune disease in which the target tissue is the neural retina. EAU is characterized by granuloma formation in the neural retina, destruction of photoreceptor cells, and blindness.1,2 The pathology of EAU in an animal model of putative autoimmune etiology serves as a model for sight-threatening posterior uveitis or panuveitis such as Vogt-Koyanagi-Harada (VKH) disease, Behcet's disease, birdshot retinochoroidopathy, sympathetic ophthalmia, and ocular sarcoidosis.3 There was a report that oxidative stress induced HO-1 exclusively in the Muller cells of mouse retina in vitro study,4 but others report that HO-1 expressed in the rat retina against light damage.5 Ohta et al.6 reported that there was a protective role of HO-1 against endotoxin-induced uveitis (EIU). They revealed HO-1 and HO-2 was expressed in iris and ciliary body (ICB). EIU is an animal model corresponds to anterior uveitis that is improved easily by topical steroid therapy. However, this study is first time to disclose that HO-1 has an important role against EAU that correspond to posterior uveitis. Oxidative stress is the fundamental mechanism underlying many different diseases, and is implicated in the pathogenesis of many neurological pathologies. Organisms use a multitude of endogenous antioxidant mechanisms to defend against the deleterious effects of oxidative stress. Heme oxygenase-1 (HO-1) is one such potent mechanism. HO-1 protein, also called heat shock protein 32 (hsp32), is the rate-limiting enzyme in the catabolism of heme to biliverdin, free iron, and CO. Its expression has been correlated with protection against oxidative stress and ischemia. HO-1 activity is increased in whole animal tissues and in cultured cells following treatment with heme, metals, and inflammatory cytokines, as well as under hypoxic and oxidative conditions. HO-1 is also induced by various stimuli, including heat shock, hyperoxia, and oxidative stress, and represents a powerful endogenous protective mechanism against free radicals in a variety of pathological conditions, including inflammation, ischemic stroke, and many neurodegenerative diseases.7 Hemin is an iron containing metalloporphyrin. Chemically, hemin is represented as chloro (7,12-diethenyl-3,8,13,17-tetramethyl-21H, 23H-porphine 2,18-dipropanoato (2-) -N21, N22, N23, N24) iron. Hemin is substrate for the HO-1 enzyme. HO enzyme is up-regulated by its substrate hemin.8 SnPP is tin-protophophyrin IX, a potent competitive inhibitor of HO, regulates HO by a dual control mechanism that is potently inhibiting the HO enzyme activity while enhancing the synthesis of HO enzyme protein.9 In this study, we examined the expression of HO-1 in lesions of EAU to evaluate the involvement of HO-1 in EAU, and demonstrated that hemin, an inducer of HO-1, ameliorates EAU clinically. To confirm these clinical effects, histological, western blotting, and immunohistochemical analyses of HO-1 were performed.