Prevention of posterior capsular opacification through aldose reductase inhibition

Umesh C S Yadav, Farshid Ighani-Hosseinabad, Frederik J G M Van Kuijk, Satish Srivastava, Kota Ramana

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

PURPOSE. The purpose of this study was to evaluate the effect of aldose reductase (AR) inhibition on posterior capsular opacification (PCO) with the use of a pig eye capsular bag model. METHODS. Pig eye capsular bags were prepared by capsulorhexis and cultured in medium without or with AR inhibitors for 7 days. Immunostaining was performed in paraformaldehyde-fixed capsular bags to determine the expression of proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (SMA), β-crystallin, and intercellular adhesion molecule (ICAM)-1. The effect of AR inhibition on basic fibroblast growth factor (BFGF)-induced mitogenic signaling in cultured human lens epithelial cells (HLECs) was examined. Cell growth was assessed by 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and cell counting, the expression of α-SMA, β-crystallin, and ICAM-1 by Western blot and immunocytochemical analysis, protein kinases by Western blot analysis, and NF-κB activation by gel shift and reporter assays. RESULTS. During culture of pig eye capsular bags, residual cells on both the anterior and the posterior capsule showed vigorous growth. Treatment with AR inhibitors significantly prevented the lens epithelial cell growth in capsular bags and expression of α-SMA, β-crystallin, and ICAM-1. HLECs showed a dose-dependent response to BFGF, proliferation at lower concentrations (<20 ng/mL) and differentiation/transdifferentiation at higher concentrations (>50 ng/mL). Inhibition of AR also prevented the BFGF-induced activation of ERK1/2, JNK, and NF-κB in HLECs. CONCLUSIONS. Results suggest that AR is required for lens epithelial cell growth and differentiation/transdifferentiation in the capsular bags, indicating that inhibition of AR could be a potential therapeutic target in the prevention of PCO.

Original languageEnglish (US)
Pages (from-to)752-759
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume50
Issue number2
DOIs
StatePublished - Feb 2009

Fingerprint

Aldehyde Reductase
Lenses
Epithelial Cells
Crystallins
Fibroblast Growth Factor 2
Intercellular Adhesion Molecule-1
Smooth Muscle
Actins
Swine
Growth
Western Blotting
Capsulorhexis
Proliferating Cell Nuclear Antigen
Protein Kinases
Capsules
Cell Differentiation
Gels

ASJC Scopus subject areas

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

Cite this

Prevention of posterior capsular opacification through aldose reductase inhibition. / Yadav, Umesh C S; Ighani-Hosseinabad, Farshid; Van Kuijk, Frederik J G M; Srivastava, Satish; Ramana, Kota.

In: Investigative Ophthalmology and Visual Science, Vol. 50, No. 2, 02.2009, p. 752-759.

Research output: Contribution to journalArticle

Yadav, Umesh C S ; Ighani-Hosseinabad, Farshid ; Van Kuijk, Frederik J G M ; Srivastava, Satish ; Ramana, Kota. / Prevention of posterior capsular opacification through aldose reductase inhibition. In: Investigative Ophthalmology and Visual Science. 2009 ; Vol. 50, No. 2. pp. 752-759.
@article{3fe031514a2a4961a0582924e08e3b95,
title = "Prevention of posterior capsular opacification through aldose reductase inhibition",
abstract = "PURPOSE. The purpose of this study was to evaluate the effect of aldose reductase (AR) inhibition on posterior capsular opacification (PCO) with the use of a pig eye capsular bag model. METHODS. Pig eye capsular bags were prepared by capsulorhexis and cultured in medium without or with AR inhibitors for 7 days. Immunostaining was performed in paraformaldehyde-fixed capsular bags to determine the expression of proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (SMA), β-crystallin, and intercellular adhesion molecule (ICAM)-1. The effect of AR inhibition on basic fibroblast growth factor (BFGF)-induced mitogenic signaling in cultured human lens epithelial cells (HLECs) was examined. Cell growth was assessed by 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and cell counting, the expression of α-SMA, β-crystallin, and ICAM-1 by Western blot and immunocytochemical analysis, protein kinases by Western blot analysis, and NF-κB activation by gel shift and reporter assays. RESULTS. During culture of pig eye capsular bags, residual cells on both the anterior and the posterior capsule showed vigorous growth. Treatment with AR inhibitors significantly prevented the lens epithelial cell growth in capsular bags and expression of α-SMA, β-crystallin, and ICAM-1. HLECs showed a dose-dependent response to BFGF, proliferation at lower concentrations (<20 ng/mL) and differentiation/transdifferentiation at higher concentrations (>50 ng/mL). Inhibition of AR also prevented the BFGF-induced activation of ERK1/2, JNK, and NF-κB in HLECs. CONCLUSIONS. Results suggest that AR is required for lens epithelial cell growth and differentiation/transdifferentiation in the capsular bags, indicating that inhibition of AR could be a potential therapeutic target in the prevention of PCO.",
author = "Yadav, {Umesh C S} and Farshid Ighani-Hosseinabad and {Van Kuijk}, {Frederik J G M} and Satish Srivastava and Kota Ramana",
year = "2009",
month = "2",
doi = "10.1167/iovs.08-2322",
language = "English (US)",
volume = "50",
pages = "752--759",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "2",

}

TY - JOUR

T1 - Prevention of posterior capsular opacification through aldose reductase inhibition

AU - Yadav, Umesh C S

AU - Ighani-Hosseinabad, Farshid

AU - Van Kuijk, Frederik J G M

AU - Srivastava, Satish

AU - Ramana, Kota

PY - 2009/2

Y1 - 2009/2

N2 - PURPOSE. The purpose of this study was to evaluate the effect of aldose reductase (AR) inhibition on posterior capsular opacification (PCO) with the use of a pig eye capsular bag model. METHODS. Pig eye capsular bags were prepared by capsulorhexis and cultured in medium without or with AR inhibitors for 7 days. Immunostaining was performed in paraformaldehyde-fixed capsular bags to determine the expression of proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (SMA), β-crystallin, and intercellular adhesion molecule (ICAM)-1. The effect of AR inhibition on basic fibroblast growth factor (BFGF)-induced mitogenic signaling in cultured human lens epithelial cells (HLECs) was examined. Cell growth was assessed by 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and cell counting, the expression of α-SMA, β-crystallin, and ICAM-1 by Western blot and immunocytochemical analysis, protein kinases by Western blot analysis, and NF-κB activation by gel shift and reporter assays. RESULTS. During culture of pig eye capsular bags, residual cells on both the anterior and the posterior capsule showed vigorous growth. Treatment with AR inhibitors significantly prevented the lens epithelial cell growth in capsular bags and expression of α-SMA, β-crystallin, and ICAM-1. HLECs showed a dose-dependent response to BFGF, proliferation at lower concentrations (<20 ng/mL) and differentiation/transdifferentiation at higher concentrations (>50 ng/mL). Inhibition of AR also prevented the BFGF-induced activation of ERK1/2, JNK, and NF-κB in HLECs. CONCLUSIONS. Results suggest that AR is required for lens epithelial cell growth and differentiation/transdifferentiation in the capsular bags, indicating that inhibition of AR could be a potential therapeutic target in the prevention of PCO.

AB - PURPOSE. The purpose of this study was to evaluate the effect of aldose reductase (AR) inhibition on posterior capsular opacification (PCO) with the use of a pig eye capsular bag model. METHODS. Pig eye capsular bags were prepared by capsulorhexis and cultured in medium without or with AR inhibitors for 7 days. Immunostaining was performed in paraformaldehyde-fixed capsular bags to determine the expression of proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (SMA), β-crystallin, and intercellular adhesion molecule (ICAM)-1. The effect of AR inhibition on basic fibroblast growth factor (BFGF)-induced mitogenic signaling in cultured human lens epithelial cells (HLECs) was examined. Cell growth was assessed by 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and cell counting, the expression of α-SMA, β-crystallin, and ICAM-1 by Western blot and immunocytochemical analysis, protein kinases by Western blot analysis, and NF-κB activation by gel shift and reporter assays. RESULTS. During culture of pig eye capsular bags, residual cells on both the anterior and the posterior capsule showed vigorous growth. Treatment with AR inhibitors significantly prevented the lens epithelial cell growth in capsular bags and expression of α-SMA, β-crystallin, and ICAM-1. HLECs showed a dose-dependent response to BFGF, proliferation at lower concentrations (<20 ng/mL) and differentiation/transdifferentiation at higher concentrations (>50 ng/mL). Inhibition of AR also prevented the BFGF-induced activation of ERK1/2, JNK, and NF-κB in HLECs. CONCLUSIONS. Results suggest that AR is required for lens epithelial cell growth and differentiation/transdifferentiation in the capsular bags, indicating that inhibition of AR could be a potential therapeutic target in the prevention of PCO.

UR - http://www.scopus.com/inward/record.url?scp=59449089371&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=59449089371&partnerID=8YFLogxK

U2 - 10.1167/iovs.08-2322

DO - 10.1167/iovs.08-2322

M3 - Article

VL - 50

SP - 752

EP - 759

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 2

ER -