The gene therapy revolution in ophthalmology.
PDF (617K)
Journal: 2014/June - Saudi Journal of Ophthalmology
ISSN: 1319-4534
Abstract:
The advances in gene therapy hold significant promise for the treatment of ophthalmic conditions. Several studies using animal models have been published. Animal models on retinitis pigmentosa, Leber's Congenital Amaurosis (LCA), and Stargardt disease have involved the use of adeno-associated virus (AAV) to deliver functional genes into mice and canines. Mice models have been used to show that a mutation in cGMP phosphodiesterase that results in retinitis pigmentosa can be corrected using rAAV vectors. Additionally, rAAV vectors have been successfully used to deliver ribozyme into mice with a subsequent improvement in autosomal dominant retinitis pigmentosa. By using dog models, researchers have made progress in studying X-linked retinitis pigmentosa which results from a RPGR gene mutation. Mouse and canine models have also been used in the study of LCA. The widely studied form of LCA is LCA2, resulting from a mutation in the gene RPE65. Mice and canines that were injected with normal copies of RPE65 gene showed signs such as improved retinal pigment epithelium transduction, visual acuity, and functional recovery. Studies on Stargardt disease have shown that mutations in the ABCA4 gene can be corrected with AAV vectors, or nanoparticles. Gene therapy for the treatment of red-green color blindness was successful in squirrel monkeys. Plans are at an advanced stage to begin clinical trials. Researchers have also proved that CD59 can be used with AMD. Gene therapy is also able to treat primary open angle glaucoma (POAG) in animal models, and studies show it is economically viable.
Open in
PUBMED | DOI | PMC | Google Scholar | Wikipedia
Relations:
Content
Citations
(10)
References
(7)
Affiliates
(1)
Similar articles
Articles by the same authors
Discussion board
Saudi J Ophthalmol 27(2): 107-111
PMID: 24227970

The gene therapy revolution in ophthalmology

College of Pharmacy, Salman Bin Abdulaziz University, Al-Kharj, Saudi Arabia
Department of Pharmacy Services, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia
Fahad I. Al-Saikhan: moc.liamtoh@nahkiasf
Corresponding author. Address: Assistant Professor & Vice dean for Academic Affairs, College of Pharmacy, Salman Bin Abdulaziz University. P.O. Box 173, Al-Kharj 11942, Saudi Arabia. Tel.: +966 1 4821234x3121; fax: +966 4816226. moc.liamtoh@nahkiasf
College of Pharmacy, Salman Bin Abdulaziz University, Al-Kharj, Saudi Arabia
Department of Pharmacy Services, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia
Fahad I. Al-Saikhan: moc.liamtoh@nahkiasf
Received 2012 Sep 15; Revised 2012 Nov 6; Accepted 2013 Feb 4.
Copyright © 2013 Production and hosting by Elsevier B.V. on behalf of King Saud University.

Abstract

The advances in gene therapy hold significant promise for the treatment of ophthalmic conditions. Several studies using animal models have been published. Animal models on retinitis pigmentosa, Leber’s Congenital Amaurosis (LCA), and Stargardt disease have involved the use of adeno-associated virus (AAV) to deliver functional genes into mice and canines. Mice models have been used to show that a mutation in cGMP phosphodiesterase that results in retinitis pigmentosa can be corrected using rAAV vectors. Additionally, rAAV vectors have been successfully used to deliver ribozyme into mice with a subsequent improvement in autosomal dominant retinitis pigmentosa. By using dog models, researchers have made progress in studying X-linked retinitis pigmentosa which results from a RPGR gene mutation. Mouse and canine models have also been used in the study of LCA. The widely studied form of LCA is LCA2, resulting from a mutation in the gene RPE65. Mice and canines that were injected with normal copies of RPE65 gene showed signs such as improved retinal pigment epithelium transduction, visual acuity, and functional recovery. Studies on Stargardt disease have shown that mutations in the ABCA4 gene can be corrected with AAV vectors, or nanoparticles. Gene therapy for the treatment of red–green color blindness was successful in squirrel monkeys. Plans are at an advanced stage to begin clinical trials. Researchers have also proved that CD59 can be used with AMD. Gene therapy is also able to treat primary open angle glaucoma (POAG) in animal models, and studies show it is economically viable.

Keywords: Gene therapy, Vector, Retinitis pigmentosa, Leber’s Congenital Amaurosis (LCA), Stargardt’s ophthalmology, Age related macular degeneration (AMD), CD59, Primary open angle glaucoma (POAG)
Abstract

Footnotes

Peer review under responsibility of Saudi Ophthalmological Society, King Saud University.

An external file that holds a picture, illustration, etc. Object name is fx1.jpg

Footnotes

References

  • 1. Silva, Nuno Filipe. Gene therapy for Stargardt and other ABCA4-related diseases: lessons from the RPE65-LCA trial. School of Medicine, University of Coimbra. Web: <>; 2010 [02.08.12].[PubMed]
  • 2. MacLaren, Robert. Gene therapy. Nuffield Laboratory of Ophthalmology. <>; [21.07.12].[PubMed]
  • 3. Institute, National Cancer. Gene therapy for cancer: questions and answers. <>; [25.07.12].[PubMed]
  • 4. Mandal, Ananya. Retinitis pigmentosa genetics. News Medical. <>; [21.07.12].[PubMed]
  • 5. Frederick Fraunfelder T., Fraunfelder Frederick W., Roy Hampton F. Elsevier; Philadelphia: 2007. Fraunfelder’s current ocular therapy. [PubMed]
  • 6. Retinitis pigmentosa news and research. News medical. <>; [12.07.12].[PubMed]
  • 7. Duker Jay S., Yanoff Myron. Elsevier; Philadelphia: 2009. Ophthalmology. [PubMed]
  • 8. Nagatsu T., Parvez S.H., Bertolotti Roger. VSP; Leiden: 2000. Progress in gene therapy: basic and clinical frontiers. [PubMed]
  • 9. What is gene therapy? News medical<>; [15.07.12].[PubMed]
  • 10. Chen Haoyu, Chen Yali, Horn Rachael, Yang Zhenglin, Wang ChangguanClinical features of autosomal dominant retinitis pigmentosa associated. Ann Acad Med. 2006;35(6):412–415.[PubMed][Google Scholar]
  • 11. Hays, Dustin C. Canine study puts gene therapy for X-linked retinitis pigmentosa in sight. National Eye Institute. <>; [28.06.12].[PubMed]
  • 12. Ghosh, Pallab. Gene therapy first for poor sight. Stargardt’s Australia. <>; [26.06.12].[PubMed]
  • 13. Rolling Fabienne, Moullier Philippe, Lhériteau Elsa, Stieger KnutAAV-mediated gene therapy for retinal disorders in large animal models. ILAR J. 2009;50(2):206–224.[PubMed][Google Scholar]
  • 14. Simonelli F., Maguire A.M., Testa F., Pierce E.A., Mingozzi F., Bennicelli J.LGene therapy for Leber’s Congenital Amaurosis is safe and effective through 1.5 years after vector administration. Mol Ther. 2010;18(3):643–650.[Google Scholar]
  • 15. Acton, Ashton Q. Leber congenital amaurosis: new insights for the healthcare professional. 2011 ed. Scholarly Paper. Atlanta: Scholarly Editions; 2011.
  • 16. Mussolino C., Della Corte M., Rossi S., Viola F., Di Vicino U., Marrocc EAAV-mediated photoreceptor transduction of the pig cone-enriched retina. Gene Ther. 2011;18(7):637–645.[Google Scholar]
  • 17. Cai X., Conley S.M., Naash M.IRPE65: role in the visual cycle, human retinal disease, and gene therapy. Ophthalmic Genet. 2009;30(2):57.[Google Scholar]
  • 18. Reichsman Frieda, Fitzgerald-Hayes Molly. Academic Press; Waltham: 2009. DNA and biotechnology. [PubMed]
  • 19. Hammer, Robert. Stargardt disease. MD support. <>; [28.07.12].[PubMed]
  • 20. Nonviral DNA nanoparticles for ocular gene therapy to treat Stargardt’s disease. SciBX 5(34); doi:10.1038/scibx.2012.911. Aug. 30 2012.
  • 21. Naash, Muna. Nanoparticle-based gene therapy preserves vision in lab study for Stargardt disease. Foundation Fighting Blindness. Web: <>; [22.07.12].[PubMed]
  • 22. Dobson Jon, Yiu Humphrey H.P., McBain Stuart CMagnetic nanoparticles for gene and drug delivery. Int J Nanomedicine. 2008;3(2):169–180.[Google Scholar]
  • 23. Berezow A.B. Northwest science and technology. Gene therapy treats red-green colorblindness in adult monkeys. Spring. 2010[PubMed]
  • 24. Gullagher S. Tufts. Gene therapy shows promise against age-related macular degeneration. April 29, 2011. Web: <>; [11.05.12].[PubMed]
  • 25. Li M., Xu J., Chen X., Sun XRNA interference as a gene silencing therapy for mutant MYOC protein in primary open angle glaucoma. Diagn Pathol. 2009;4(46):4–46.[Google Scholar]
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.