Aldose reductase deficiency protects from autoimmune- and endotoxin-induced uveitis in mice

Umesh C S Yadav, Mohammed Shoeb, Satish Srivastava, Kota Ramana

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Purpose. To investigate the effect of aldose reductase (AR) deficiency in protecting the chronic experimental autoimmune (EAU) and acute endotoxin-induced uveitis (EIU) in c57BL/6 mice. Methods. The WT and AR-null (ARKO) mice were immunized with human interphotoreceptor retinoid-binding peptide (hIRPB-1-20), to induce EAU, or were injected subcutaneously with lipopolysaccharide (LPS; 100 μg) to induce EIU. The mice were killed on day 21 for EAU and at 24 hours for EIU, when the disease was at its peak, and the eyes were immediately enucleated for histologic and biochemical studies. Spleen-derived T-lymphocytes were used to study the antigen-specific immune response in vitro and in vivo. Results. In WT-EAU mice, severe damage to the retinal wall, especially to the photoreceptor layer was observed, corresponding to a pathologic score of ~2, which was significantly prevented in the ARKO or AR inhibitor-treated mice. The levels of cytokines and chemokines increased markedly in the whole-eye homogenates of WT-EAU mice, but not in ARKO-EAU mice. Further, expression of inflammatory marker proteins such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, and vascular cell adhesion molecule (VCAM)-1 was increased in the WT-EIU mouse eyes but not in the ARKO-EIU eyes. The T cells proliferated vigorously when exposed to the hIRPB antigen in vitro and secreted various cytokines and chemokines, which were significantly inhibited in the T cells isolated from the ARKO mice. Conclusions. These findings suggest that AR-deficiency/inhibition protects against acute as well as chronic forms of ocular inflammatory complications such as uveitis.

Original languageEnglish (US)
Pages (from-to)8076-8085
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number11
DOIs
StatePublished - Oct 2011

Fingerprint

Aldehyde Reductase
Uveitis
Endotoxins
T-Lymphocytes
Chemokines
Cytokines
Vascular Cell Adhesion Molecule-1
Histocompatibility Antigens Class II
Retinoids
Nitric Oxide Synthase Type II
Cyclooxygenase 2
Lipopolysaccharides
Spleen
Tumor Necrosis Factor-alpha
Antigens
Peptides

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Aldose reductase deficiency protects from autoimmune- and endotoxin-induced uveitis in mice. / Yadav, Umesh C S; Shoeb, Mohammed; Srivastava, Satish; Ramana, Kota.

In: Investigative Ophthalmology and Visual Science, Vol. 52, No. 11, 10.2011, p. 8076-8085.

Research output: Contribution to journalArticle

Yadav, Umesh C S ; Shoeb, Mohammed ; Srivastava, Satish ; Ramana, Kota. / Aldose reductase deficiency protects from autoimmune- and endotoxin-induced uveitis in mice. In: Investigative Ophthalmology and Visual Science. 2011 ; Vol. 52, No. 11. pp. 8076-8085.
@article{abbdff5abac3465c96346ce52d1f62ef,
title = "Aldose reductase deficiency protects from autoimmune- and endotoxin-induced uveitis in mice",
abstract = "Purpose. To investigate the effect of aldose reductase (AR) deficiency in protecting the chronic experimental autoimmune (EAU) and acute endotoxin-induced uveitis (EIU) in c57BL/6 mice. Methods. The WT and AR-null (ARKO) mice were immunized with human interphotoreceptor retinoid-binding peptide (hIRPB-1-20), to induce EAU, or were injected subcutaneously with lipopolysaccharide (LPS; 100 μg) to induce EIU. The mice were killed on day 21 for EAU and at 24 hours for EIU, when the disease was at its peak, and the eyes were immediately enucleated for histologic and biochemical studies. Spleen-derived T-lymphocytes were used to study the antigen-specific immune response in vitro and in vivo. Results. In WT-EAU mice, severe damage to the retinal wall, especially to the photoreceptor layer was observed, corresponding to a pathologic score of ~2, which was significantly prevented in the ARKO or AR inhibitor-treated mice. The levels of cytokines and chemokines increased markedly in the whole-eye homogenates of WT-EAU mice, but not in ARKO-EAU mice. Further, expression of inflammatory marker proteins such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, and vascular cell adhesion molecule (VCAM)-1 was increased in the WT-EIU mouse eyes but not in the ARKO-EIU eyes. The T cells proliferated vigorously when exposed to the hIRPB antigen in vitro and secreted various cytokines and chemokines, which were significantly inhibited in the T cells isolated from the ARKO mice. Conclusions. These findings suggest that AR-deficiency/inhibition protects against acute as well as chronic forms of ocular inflammatory complications such as uveitis.",
author = "Yadav, {Umesh C S} and Mohammed Shoeb and Satish Srivastava and Kota Ramana",
year = "2011",
month = "10",
doi = "10.1167/iovs.11-7830",
language = "English (US)",
volume = "52",
pages = "8076--8085",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "11",

}

TY - JOUR

T1 - Aldose reductase deficiency protects from autoimmune- and endotoxin-induced uveitis in mice

AU - Yadav, Umesh C S

AU - Shoeb, Mohammed

AU - Srivastava, Satish

AU - Ramana, Kota

PY - 2011/10

Y1 - 2011/10

N2 - Purpose. To investigate the effect of aldose reductase (AR) deficiency in protecting the chronic experimental autoimmune (EAU) and acute endotoxin-induced uveitis (EIU) in c57BL/6 mice. Methods. The WT and AR-null (ARKO) mice were immunized with human interphotoreceptor retinoid-binding peptide (hIRPB-1-20), to induce EAU, or were injected subcutaneously with lipopolysaccharide (LPS; 100 μg) to induce EIU. The mice were killed on day 21 for EAU and at 24 hours for EIU, when the disease was at its peak, and the eyes were immediately enucleated for histologic and biochemical studies. Spleen-derived T-lymphocytes were used to study the antigen-specific immune response in vitro and in vivo. Results. In WT-EAU mice, severe damage to the retinal wall, especially to the photoreceptor layer was observed, corresponding to a pathologic score of ~2, which was significantly prevented in the ARKO or AR inhibitor-treated mice. The levels of cytokines and chemokines increased markedly in the whole-eye homogenates of WT-EAU mice, but not in ARKO-EAU mice. Further, expression of inflammatory marker proteins such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, and vascular cell adhesion molecule (VCAM)-1 was increased in the WT-EIU mouse eyes but not in the ARKO-EIU eyes. The T cells proliferated vigorously when exposed to the hIRPB antigen in vitro and secreted various cytokines and chemokines, which were significantly inhibited in the T cells isolated from the ARKO mice. Conclusions. These findings suggest that AR-deficiency/inhibition protects against acute as well as chronic forms of ocular inflammatory complications such as uveitis.

AB - Purpose. To investigate the effect of aldose reductase (AR) deficiency in protecting the chronic experimental autoimmune (EAU) and acute endotoxin-induced uveitis (EIU) in c57BL/6 mice. Methods. The WT and AR-null (ARKO) mice were immunized with human interphotoreceptor retinoid-binding peptide (hIRPB-1-20), to induce EAU, or were injected subcutaneously with lipopolysaccharide (LPS; 100 μg) to induce EIU. The mice were killed on day 21 for EAU and at 24 hours for EIU, when the disease was at its peak, and the eyes were immediately enucleated for histologic and biochemical studies. Spleen-derived T-lymphocytes were used to study the antigen-specific immune response in vitro and in vivo. Results. In WT-EAU mice, severe damage to the retinal wall, especially to the photoreceptor layer was observed, corresponding to a pathologic score of ~2, which was significantly prevented in the ARKO or AR inhibitor-treated mice. The levels of cytokines and chemokines increased markedly in the whole-eye homogenates of WT-EAU mice, but not in ARKO-EAU mice. Further, expression of inflammatory marker proteins such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, and vascular cell adhesion molecule (VCAM)-1 was increased in the WT-EIU mouse eyes but not in the ARKO-EIU eyes. The T cells proliferated vigorously when exposed to the hIRPB antigen in vitro and secreted various cytokines and chemokines, which were significantly inhibited in the T cells isolated from the ARKO mice. Conclusions. These findings suggest that AR-deficiency/inhibition protects against acute as well as chronic forms of ocular inflammatory complications such as uveitis.

UR - http://www.scopus.com/inward/record.url?scp=84855385137&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855385137&partnerID=8YFLogxK

U2 - 10.1167/iovs.11-7830

DO - 10.1167/iovs.11-7830

M3 - Article

C2 - 21911582

AN - SCOPUS:84855385137

VL - 52

SP - 8076

EP - 8085

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 11

ER -