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Vol. 100, No. 4, 2011
Issue release date: November 2011
Free Access
Neonatology 2011;100:343–353
(DOI:10.1159/000330174)

Understanding Retinopathy of Prematurity: Update on Pathogenesis

Rivera J.C.a, b · Sapieha P.b · Joyal J.-S.a · Duhamel F.a, b · Shao Z.a · Sitaras N.a · Picard E.a · Zhou E.a, b · Lachapelle P.c · Chemtob S.a, b
aDepartment of Pediatrics, Ophthalmology and Pharmacology, Centre Hospitalier Universitaire Sainte-Justine Research Center, bDepartment of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center, University of Montreal, and cDepartment of Ophthalmology/Neurology, McGill University-Montreal Children’s Hospital Research Institute, Montréal, Qué., Canada
email Corresponding Author

Abstract

Retinopathy of prematurity (ROP), an ocular disease characterized by the onset of vascular abnormalities in the developing retina, is the major cause of visual impairment and blindness in premature neonates. ROP is a complex condition in which various factors participate at different stages of the disease leading to microvascular degeneration followed by neovascularization, which in turn predisposes to retinal detachment. Current ablative therapies (cryotherapy and laser photocoagulation) used in the clinic for the treatment of ROP have limitations and patients can still have long-term effects even after successful treatment. New treatment modalities are still emerging. The most promising are the therapies directed against VEGF; more recently the use of preventive dietary supplementation with ω-3 polyunsaturated fatty acid may also be promising. Other than pharmacologic and nutritional approaches, cell-based strategies for vascular repair are likely to arise from advances in regenerative medicine using stem cells. In addition to all of these, a greater understanding of other factors involved in regulating pathologic retinal angiogenesis continues to emerge, suggesting potential targets for therapeutic approaches. This review summarizes an update on the current state of knowledge on ROP from our and other laboratories, with particular focus on the role of nitro-oxidative stress and notably trans-arachidonic acids in microvascular degeneration, semaphorin 3 operating as vasorepulsive molecules in the avascular hypoxic retina and in turn impairing revascularization, succinate and its receptor GPR91 in neuron-mediated retinal neovascularization, and ω-3 lipids as modulators of preretinal neovascularization.


 goto top of outline Key Words

  • Retinopathy
  • Nitro-oxidative stress
  • Trans-arachidonic acids
  • Succinate
  • GPR91
  • Semaphorin 3A and 3E
  • ω-3 lipids

 goto top of outline Abstract

Retinopathy of prematurity (ROP), an ocular disease characterized by the onset of vascular abnormalities in the developing retina, is the major cause of visual impairment and blindness in premature neonates. ROP is a complex condition in which various factors participate at different stages of the disease leading to microvascular degeneration followed by neovascularization, which in turn predisposes to retinal detachment. Current ablative therapies (cryotherapy and laser photocoagulation) used in the clinic for the treatment of ROP have limitations and patients can still have long-term effects even after successful treatment. New treatment modalities are still emerging. The most promising are the therapies directed against VEGF; more recently the use of preventive dietary supplementation with ω-3 polyunsaturated fatty acid may also be promising. Other than pharmacologic and nutritional approaches, cell-based strategies for vascular repair are likely to arise from advances in regenerative medicine using stem cells. In addition to all of these, a greater understanding of other factors involved in regulating pathologic retinal angiogenesis continues to emerge, suggesting potential targets for therapeutic approaches. This review summarizes an update on the current state of knowledge on ROP from our and other laboratories, with particular focus on the role of nitro-oxidative stress and notably trans-arachidonic acids in microvascular degeneration, semaphorin 3 operating as vasorepulsive molecules in the avascular hypoxic retina and in turn impairing revascularization, succinate and its receptor GPR91 in neuron-mediated retinal neovascularization, and ω-3 lipids as modulators of preretinal neovascularization.

Copyright © 2011 S. Karger AG, Basel


 goto top of outline References
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 goto top of outline Author Contacts

Sylvain Chemtob, MD, PhD, FRCPC
Department of Pediatrics, Ophthalmology and Pharmacology
Centre Hospitalier Universitaire Sainte-Justine Research Center
3175, Chemin Côte Sainte-Catherine, Montréal, QC H3T 1C5 (Canada)
Tel. +1 514 345 4931, ext. 2978, E-Mail sylvain.chemtob@umontreal.ca


 goto top of outline Article Information

Presented at the International Symposium ‘Recent Advances in Neonatal Medicine’, Würzburg, 2011.

Published online: October 3, 2011
Number of Print Pages : 11
Number of Figures : 4, Number of Tables : 0, Number of References : 76


 goto top of outline Publication Details

Neonatology (Fetal and Neonatal Research)

Vol. 100, No. 4, Year 2011 (Cover Date: November 2011)

Journal Editor: Halliday H.L. (Belfast), Speer C.P. (Würzburg)
ISSN: 1661-7800 (Print), eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Retinopathy of prematurity (ROP), an ocular disease characterized by the onset of vascular abnormalities in the developing retina, is the major cause of visual impairment and blindness in premature neonates. ROP is a complex condition in which various factors participate at different stages of the disease leading to microvascular degeneration followed by neovascularization, which in turn predisposes to retinal detachment. Current ablative therapies (cryotherapy and laser photocoagulation) used in the clinic for the treatment of ROP have limitations and patients can still have long-term effects even after successful treatment. New treatment modalities are still emerging. The most promising are the therapies directed against VEGF; more recently the use of preventive dietary supplementation with ω-3 polyunsaturated fatty acid may also be promising. Other than pharmacologic and nutritional approaches, cell-based strategies for vascular repair are likely to arise from advances in regenerative medicine using stem cells. In addition to all of these, a greater understanding of other factors involved in regulating pathologic retinal angiogenesis continues to emerge, suggesting potential targets for therapeutic approaches. This review summarizes an update on the current state of knowledge on ROP from our and other laboratories, with particular focus on the role of nitro-oxidative stress and notably trans-arachidonic acids in microvascular degeneration, semaphorin 3 operating as vasorepulsive molecules in the avascular hypoxic retina and in turn impairing revascularization, succinate and its receptor GPR91 in neuron-mediated retinal neovascularization, and ω-3 lipids as modulators of preretinal neovascularization.



 goto top of outline Author Contacts

Sylvain Chemtob, MD, PhD, FRCPC
Department of Pediatrics, Ophthalmology and Pharmacology
Centre Hospitalier Universitaire Sainte-Justine Research Center
3175, Chemin Côte Sainte-Catherine, Montréal, QC H3T 1C5 (Canada)
Tel. +1 514 345 4931, ext. 2978, E-Mail sylvain.chemtob@umontreal.ca


 goto top of outline Article Information

Presented at the International Symposium ‘Recent Advances in Neonatal Medicine’, Würzburg, 2011.

Published online: October 3, 2011
Number of Print Pages : 11
Number of Figures : 4, Number of Tables : 0, Number of References : 76


 goto top of outline Publication Details

Neonatology (Fetal and Neonatal Research)

Vol. 100, No. 4, Year 2011 (Cover Date: November 2011)

Journal Editor: Halliday H.L. (Belfast), Speer C.P. (Würzburg)
ISSN: 1661-7800 (Print), eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Terry TL: Extreme prematurity and fibroplastic overgrowth of persistent vascular sheath behind each crystalline lens. I. Preliminary report. Am J Ophthalmol 1942;25:203–204.
  2. Chen J, Smith LE: Retinopathy of prematurity. Angiogenesis 2007;10:133–140.
  3. Mintz-Hittner HA, Kennedy KA, Chuang AZ; BEAT-ROP Cooperative Group: Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med 2011;364:603–615.
  4. Penn JS, Tolman BL, Henry MM: Oxygen-induced retinopathy in the rat: relationship of retinal nonperfusion to subsequent neovascularization. Invest Ophthalmol Vis Sci 1994;35:3429–3435.
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