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Article: Synergistic effect of osmotic and oxidative stress in slow-developing cataract formation

TitleSynergistic effect of osmotic and oxidative stress in slow-developing cataract formation
Authors
Keywordscataract
diabetes
osmotic stress
oxidative stress
sorbitol dehydrogenase
vitamin E
Issue Date2008
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yexer
Citation
Experimental Eye Research, 2008, v. 87 n. 5, p. 454-461 How to Cite?
AbstractDiabetes is a major contributing factor in cataract development. In animal models where cataracts develop within days or weeks of diabetes it is well established that osmotic stress from the accumulation of sorbitol leads to cataract development. This mechanism might explain the rare cases of acute cataract sometimes found in patients with uncontrolled sustained hyperglycemia but cannot account for the vast majority of cataracts that developed after years of diabetes. Thus, a model that can simulate diabetic slow-developing cataract is needed. The contribution of osmotic and oxidative stress in cataract development in sorbitol dehydrogenase (SDH) deficient mice, a model for slow-developing cataract in diabetic patients was determined. Contribution of osmotic stress was assessed by HPLC measurement of sorbitol and by observing the effect of blocking sorbitol accumulation by aldose reductase (AR) null mutation in the SDH deficient mice. Contribution of oxidative stress was assessed by observing the effect of vitamin E treatment and the effect of null mutation of glutathione peroxidase-1 (Gpx-1) on cataract development in these mice. Lenticular sorbitol level was significantly increased in the SDH deficient mice, and blocking sorbitol accumulation by the AR null mutation prevented cataract development, demonstrating the contribution of osmotic stress in cataract development. SDH deficiency did not affect lens oxidative stress status. However, treatment with vitamin E significantly reduced the incidence of cataract, and Gpx-1 deficiency exacerbated cataract development in these mice. Our findings suggest that chronic oxidative stress impaired the osmoregulatory mechanism of the lens. This was not evident until modest increases in lens sorbitol increased the demand of its osmoregulatory function. This osmoregulatory dysfunction model is supported by the fact that the activity of Na +/K +-ATPase, the key regulator of cellular ions and water balance, was dramatically reduced in the precataractous lenses of the SDH deficient mice, and that treatment with vitamin E prevented the loss of Na +/K +-ATPase activity. This osmoregulatory dysfunction model might explain why diabetic patients who control their blood glucose moderately well are still susceptible to develop cataract. © 2008 Elsevier Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/58194
ISSN
2015 Impact Factor: 2.998
2015 SCImago Journal Rankings: 1.218
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grant CouncilHKU 7390/04M
Funding Information:

Work reported here was supported by Hong Kong Research Grant Council (HKU 7390/04M).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorChan, AWHen_HK
dc.contributor.authorHo, Ysen_HK
dc.contributor.authorChung, SKen_HK
dc.contributor.authorChung, SSMen_HK
dc.date.accessioned2010-05-31T03:25:35Z-
dc.date.available2010-05-31T03:25:35Z-
dc.date.issued2008en_HK
dc.identifier.citationExperimental Eye Research, 2008, v. 87 n. 5, p. 454-461en_HK
dc.identifier.issn0014-4835en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58194-
dc.description.abstractDiabetes is a major contributing factor in cataract development. In animal models where cataracts develop within days or weeks of diabetes it is well established that osmotic stress from the accumulation of sorbitol leads to cataract development. This mechanism might explain the rare cases of acute cataract sometimes found in patients with uncontrolled sustained hyperglycemia but cannot account for the vast majority of cataracts that developed after years of diabetes. Thus, a model that can simulate diabetic slow-developing cataract is needed. The contribution of osmotic and oxidative stress in cataract development in sorbitol dehydrogenase (SDH) deficient mice, a model for slow-developing cataract in diabetic patients was determined. Contribution of osmotic stress was assessed by HPLC measurement of sorbitol and by observing the effect of blocking sorbitol accumulation by aldose reductase (AR) null mutation in the SDH deficient mice. Contribution of oxidative stress was assessed by observing the effect of vitamin E treatment and the effect of null mutation of glutathione peroxidase-1 (Gpx-1) on cataract development in these mice. Lenticular sorbitol level was significantly increased in the SDH deficient mice, and blocking sorbitol accumulation by the AR null mutation prevented cataract development, demonstrating the contribution of osmotic stress in cataract development. SDH deficiency did not affect lens oxidative stress status. However, treatment with vitamin E significantly reduced the incidence of cataract, and Gpx-1 deficiency exacerbated cataract development in these mice. Our findings suggest that chronic oxidative stress impaired the osmoregulatory mechanism of the lens. This was not evident until modest increases in lens sorbitol increased the demand of its osmoregulatory function. This osmoregulatory dysfunction model is supported by the fact that the activity of Na +/K +-ATPase, the key regulator of cellular ions and water balance, was dramatically reduced in the precataractous lenses of the SDH deficient mice, and that treatment with vitamin E prevented the loss of Na +/K +-ATPase activity. This osmoregulatory dysfunction model might explain why diabetic patients who control their blood glucose moderately well are still susceptible to develop cataract. © 2008 Elsevier Ltd. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yexeren_HK
dc.relation.ispartofExperimental Eye Researchen_HK
dc.subjectcataracten_HK
dc.subjectdiabetesen_HK
dc.subjectosmotic stressen_HK
dc.subjectoxidative stressen_HK
dc.subjectsorbitol dehydrogenaseen_HK
dc.subjectvitamin Een_HK
dc.subject.meshAging - metabolism-
dc.subject.meshCataract - etiology - metabolism - physiopathology - prevention and control-
dc.subject.meshDiabetes Mellitus, Experimental - complications - metabolism - physiopathology-
dc.subject.meshOsmosis - physiology-
dc.subject.meshOxidative Stress - physiology-
dc.titleSynergistic effect of osmotic and oxidative stress in slow-developing cataract formationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0014-4835&volume=87&spage=454&epage=461&date=2008&atitle=Synergistic+effect+of+osmotic+and+oxidative+stress+in+slow-developing+cataract+formationen_HK
dc.identifier.emailChung, SK: skchung@hkucc.hku.hken_HK
dc.identifier.emailChung, SSM: smchung@hkucc.hku.hken_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.identifier.authorityChung, SSM=rp00376en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.exer.2008.08.001en_HK
dc.identifier.pmid18760274-
dc.identifier.scopuseid_2-s2.0-54249106690en_HK
dc.identifier.hkuros162826en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-54249106690&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume87en_HK
dc.identifier.issue5en_HK
dc.identifier.spage454en_HK
dc.identifier.epage461en_HK
dc.identifier.isiWOS:000261020700008-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectAldose reductase in diabetic cataract-
dc.identifier.scopusauthoridChan, AWH=55465279200en_HK
dc.identifier.scopusauthoridHo, Ys=7402555072en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK
dc.identifier.scopusauthoridChung, SSM=14120761600en_HK

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