Amelioration of Experimental Autoimmune Uveoretinitis by Aldose Reductase Inhibition in Lewis Rats

Yadav, Umesh C.S.; Mohammed, Sabira; Srivastava, Satish K.; Ramana, Kota V.

doi:10.1167/iovs.11-7485

Cited by 13 publications

(15 citation statements)

References 60 publications

(54 reference statements)

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“…For histopathologic evaluation, the iris-ciliary body complex, anterior chamber, vitreous, and retina were observed under a light microscope. Based on the number and extent of lesions seen in the HE-staining section, histological scores were provided on a scale of 0 to 4 using criteria described previously [ 17 , 19 ].…”

Section: Methodsmentioning

confidence: 99%

SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis)

Mattapallil

Sun

et al. 2016

Mediators of Inflammation

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Uveitis is a potentially sight-threatening disease characterized by repeated cycles of remission and recurrent inflammation. The JAK/STAT pathway regulates the differentiation of pathogenic Th1 and Th17 cells that mediate uveitis. A SOCS1 mimetic peptide (SOCS1-KIR) that inhibits JAK2/STAT1 pathways has recently been shown to suppress experimental autoimmune uveitis (EAU). However, it is not clear whether SOCS1-KIR ameliorated uveitis by targeting JAK/STAT pathways of pathogenic lymphocytes or via inhibition of macrophages and antigen-presenting cells that also enter the retina during EAU. To further investigate mechanisms that mediate SOCS1-KIR effects and evaluate the efficacy of SOCS1-KIR as an investigational drug for chronic uveitis, we induced EAU in rats by adoptive transfer of uveitogenic T-cells and monitored disease progression and severity by slit-lamp microscopy, histology, and optical coherence tomography. Topical administration of SOCS1-KIR ameliorated acute and chronic posterior uveitis by inhibiting Th17 cells and the recruitment of inflammatory cells into retina while promoting expansion of IL-10-producing Tregs. We further show that SOCS1-KIR conferred protection of resident retinal cells that play critical role in vision from cytotoxic effects of inflammatory cytokines by downregulating proapoptotic genes. Thus, SOCS1-KIR suppresses uveitis and confers neuroprotective effects and might be exploited as a noninvasive treatment for chronic uveitis.

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Section: Methodsmentioning

confidence: 99%

SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis)

Mattapallil

Sun

et al. 2016

Mediators of Inflammation

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“…Since these drugs have already passed in the Food and Drug Administration (FDA)'s phase I and II clinical trials and have been found to be safe without any major irreversible side effects, and it is expected that ARI such as fidarestat could be developed as novel therapy for preventing ocular inflammation especially uveitis in a relatively shorter time. [92][93][94]…”

Section: Future Directionsmentioning

confidence: 99%

New Treatment Modalities for Ocular Complications of Endocarditis

Şahin¹

2013

Recent Advances in Infective Endocarditis

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“…Uveitis, the inflammation of the uvea in the eye, is among the leading causes of blindness and vision loss in the world [ 1 – 4 ]. This disease affects people of all ages, gender, and race, though sex preponderance can be observed in some cases [ 3 , 4 ]. It also affects the working population between 20 and 59 years [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…This pathology is characterized by elevated levels of proinflammatory cytokines in ocular tissue, which involve the production of inflammatory molecules and reactive oxygen species (ROS) [ 7 ]. The experimental animal model closest to human uveitis is the acute form of bacterial endotoxin, lipopolysaccharide- (LPS-) induced uveitis (EIU) [ 3 , 4 , 8 ]. LPS increases the systemic expression of several inflammatory molecules such as TNF- α , IL-6, MIF, IFN- γ , and MCP-1 and the production of nitric oxide.…”

Section: Introductionmentioning

confidence: 99%

“…The literature reports that the inhibition of aldose reductase (AR), a key enzyme of the polyol pathway able to convert the excess glucose into sorbitol with the consequent formation of ROS, prevents or decreases the acute form of the ocular inflammation induced by LPS in rats, through decreased oxidative stress signals [ 10 ]. Various aldose reductase inhibitors (ARIs) have been tested against uveitis [ 3 , 4 , 7 , 11 – 13 ]. We recently identified a novel class of nonhydantoin noncarboxylic acid inhibitors, featuring the benzofuroxane core [ 14 , 15 ] as new scaffold interacting with the so-called AR anion site.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Ocular Aldose Reductase by a New Benzofuroxane Derivative Ameliorates Rat Endotoxic Uveitis

Filippo

Zippo

Maisto

et al. 2014

Mediators of Inflammation

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The study investigated the effects of the aldose reductase (AR) inhibitor benzofuroxane derivative 5(6)-(benzo[d]thiazol-2-ylmethoxy) benzofuroxane (herein referred to as BF-5m) on the biochemical and tissue alterations induced by endotoxic uveitis in rats. BF-5m has been administered directly into the vitreous, in order to assess the expression and levels of (i) inflammatory markers such as the ocular ubiquitin-proteasome system, NF-κB, TNF-α, and MCP-1; (ii) prooxidant and antioxidant markers such as nitrotyrosine, manganese superoxide dismutase (MnSOD), and glutathione peroxidase (GPX); (iii) apoptotic/antiapoptotic factors caspases and Bcl-xl; (iv) markers of endothelial progenitor cells (EPCs) recruitment such as CD34 and CD117. 5 μL of BF-5m (0.01; 0.05; and 0.1 μM) into the right eye decreased in a dose-dependent manner the LPS-induced inflammation of the eye, reporting a clinical score 1. It reduced the ocular levels of ubiquitin, 20S and 26S proteasome subunits, NF-κB subunits, TNF-α, MCP-1, and nitrotyrosine. BF-5m ameliorated LPS-induced decrease in levels of MnSOD and GPX. Antiapoptotic effects were seen from BF-5m by monitoring the expression of Bcl-xl, an antiapoptotic protein. Similarly, BF-5m increased recruitment of the EPCs within the eye, as evidenced by CD34 and CD117 antibodies.

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Amelioration of Experimental Autoimmune Uveoretinitis by Aldose Reductase Inhibition in Lewis Rats

Abstract: These results suggest that AR could be a novel mediator of bovine IRBP-induced uveitis in rats.

Cited by 13 publications

References 60 publications

SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis)

SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis)

New Treatment Modalities for Ocular Complications of Endocarditis

Inhibition of Ocular Aldose Reductase by a New Benzofuroxane Derivative Ameliorates Rat Endotoxic Uveitis

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