PDF herunterladen
Klin Monbl Augenheilkd 2012; 229(6): 603-607
DOI: 10.1055/s-0032-1312914
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Gentherapie in der Ophthalmologie: Stand der Forschung

Gene Therapy in Ophthalmology: State of the Art
A. Kovtun
1   Institut für Anorganische Chemie, Universität Duisburg-Essen
,
M. Epple
2   Anorganische Chemie und Center for Nanointegration Duisburg-Essen (CeNIDE), Universität Duisburg-Essen
,
K. P. Steuhl
3   Klinik für Erkrankungen des vorderen Augenabschnitts, Universitäts-Augenklinik
,
S. Erguen
4   Anatomie und Zellbiologie II, Julius-Maximilians-Universität Würzburg
,
T. Fuchsluger
5   Augenklinik, Universitätsklinikum Düsseldorf
› Institutsangaben
Weitere Informationen

Publikationsverlauf

26. April 2012

14. Mai 2012

Publikationsdatum:
29. Juni 2012 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Zusammenfassung

Der Begriff „Gentherapie“ beschreibt das Einbringen von Genen in Zellen zur Behandlung von Erkrankungen oder Gendefekten. Dazu werden Träger (Vektoren) verwendet, die diese genetischen Informationen in Zellen einschleusen. Auf diese Weise wird eine Überexpression des jeweiligen Proteins induziert oder inhibiert. Aufgrund der Möglichkeit zur visuellen Kontrolle, seines anatomischen Aufbaus und der Trennung der Blutversorgung durch die Blut-Retina-Schranke stellt das Auge ein sehr attraktives Organ für gentherapeutische Behandlungen dar. Diese Arbeit gibt einen Überblick über Fortschritte und Aussichten der Gentherapie im Fach Ophthalmologie in den letzten 10 Jahren.

Abstract

The term „gene therapy” denotes the treatment of diseases or gene deficiencies by introduction of genes into cells. To achieve this goal, vectors are used to transfer the genetic information into the cells. Thus, the protein of interest can be overexpressed or silenced. On account of its easy accessibility, the good compartmentalisation and the separation from the main bloodstream by the blood-retina barrier, the eye represents a very attractive target to treat ocular diseases by gene therapy. In this work, we provide an overview of the progress in ocular gene therapy over the last decade and give an outlook on future developments.

Schlüsselwörter

Gentherapie - Nanopartikel - Netzhaut - Hornhaut - Transduktion

Key words

gene therapy - nanoparticles - Retina - Cornea - transduction
 

  • Literatur

  • 1 Graham FL, van der Eb AJ. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 1973; 52: 456-467
    CrossrefPubMedGoogle Scholar
  • 2 Sokolova V, Epple M. Inorganic nanoparticles as carriers of nucleic acids into cells. Angew Chem Int Ed 2008; 47: 1382-1395
    CrossrefPubMedGoogle Scholar
  • 3 Conley SM, Naash MI. Nanoparticles for retinal gene therapy. Prog Retin Eye Res 2010; 29: 376-397
    CrossrefPubMedGoogle Scholar
  • 4 Jung HJ, Chauhan A. Temperature sensitive contact lenses for triggered ophthalmic drug delivery. Biomaterials 2012; 33: 2289-2300
    CrossrefPubMedGoogle Scholar
  • 5 Sakamoto T, Ikeda Y, Yonemitsu Y. Gene targeting to the retina. Adv Drug Deliv Rev 2001; 52: 93-102
    CrossrefPubMedGoogle Scholar
  • 6 Campochiaro PA. Gene transfer for neovascular age-related macular degeneration. Hum Gene Ther 2011; 22: 523-529
    CrossrefPubMedGoogle Scholar
  • 7 Neumann S, Kovtun A, Dietzel ID et al. The use of size-defined DNA-functionalized calcium phosphate nanoparticles to minimise intracellular calcium disturbance during transfection. Biomaterials 2009; 30: 6794-6802
    CrossrefPubMedGoogle Scholar
  • 8 Sokolova V, Kovtun A, Prymak O et al. Functionalisation of calcium phosphate nanoparticles by oligonucleotides and their application to gene silencing. J Mater Chem 2007; 17: 721-727
    CrossrefPubMedGoogle Scholar
  • 9 Campochiaro PA. Gene therapy for ocular neovascularization. Curr Gene Ther 2007; 7: 25-33
    CrossrefPubMedGoogle Scholar
  • 10 Naik R, Mukhopadhyay A, Ganguli M. Gene delivery to the retina: focus on non-viral approaches. Drug Discov Today 2009; 14: 306-315
    CrossrefPubMedGoogle Scholar
  • 11 Sharma A, Tandon A, Tovey JCK et al. Polyethylenimine-conjugated gold nanoparticles: Gene transfer potential and low toxicity in the cornea. Nanomedicine: Nanotechnology, Biology and Medicine 2011; DOI: 10.1016/j.nano.2011.01.006.
    PubMedGoogle Scholar
  • 12 Hu J, Kovtun A, Tomaszewski A et al. A new tool for the transfection of corneal endothelial cells: calcium phosphate nanoparticles. Acta Biomater 2011; DOI: 10.1016/j.actbio.2011.09.013.
    PubMedGoogle Scholar
  • 13 Farjo R, Skaggs J, Quiambao AB et al. Efficient non-viral ocular gene transfer with compacted DNA nanoparticles. PLoS One 2006; 1: e38 DOI: 10.1371/journal.pone.0000038.
    CrossrefPubMedGoogle Scholar
  • 14 Bundenz DL, Bennett J, Alonso L et al. In vivo gene transfer into murine corneal ednothelial and trabecular meshwork cells. Invest Ophthalmol Vis Sci 1995; 36: 2211-2215
    PubMedGoogle Scholar
  • 15 Bessis N, Garcia Cozar FJ, Boissier MC. Immune responses to gene therapy vectors: Influence on vector function and effector mechanisms. Gene Ther 2004; 11: S10-S17
    CrossrefPubMedGoogle Scholar
  • 16 Auricchio A, Rivera VM, Clackson T et al. Pharmacological regulation of protein expression from adeno-associated viral vectors in the eye. Mol Ther 2002; 6 DOI: 10.1006/mthe.2002.0660.
    PubMedGoogle Scholar
  • 17 Lai YKY, Shen WY, Brankov M et al. Potential long-term inhibition of ocular neovascularisation by recombinant adeno-associated virus-mediated secretion gene therapy. Gene Ther 2002; 9: 804-813
    CrossrefPubMedGoogle Scholar
  • 18 Bainbridge JWB, Tan MH, Ali RR. Gene therapy progress and prospects: the eye. Gene Ther 2006; 13: 1191-1197
    CrossrefPubMedGoogle Scholar
  • 19 van den Haute C, Eggermont K, Nuttin B et al. Lentiviral vector-mediated delivery of short hairpin RNA results in persistent knockdown of gene expression in mouse brain. Hum Gene Ther 2003; 14: 1799-1807
    CrossrefPubMedGoogle Scholar
  • 20 Fuchsluger TA, Jurkunas U, Kazlauskas A et al. Anti-apoptotic gene therapy prolongs survival of corneal endothelial cells during storage. Gene Ther 2011; DOI: 10.1038/gt.2011.20.
    PubMedGoogle Scholar
  • 21 Fuchsluger TA, Jurkunas U, Kazlauskas A et al. Corneal endothelial cells are protected from apoptosis by gene therapy. Hum Gene Ther 2011; 22: 549-558
    CrossrefPubMedGoogle Scholar
  • 22 Jo DH, Lee TG, Kim JH. Nanotechnology and nanotoxicology in retinopathy. Int J Mol Sci 2011; 12: 8288-8301
    CrossrefPubMedGoogle Scholar
  • 23 Cai X, Conley S, Naash M. Nanoparticle applications in ocular gene therapy. Vision Res 2008; 48: 319-324
    CrossrefPubMedGoogle Scholar
  • 24 Mori K, Gehlbach P, Yamamoto S et al. AAV-mediated gene transfer of pigment epithelium-derived factor inhibits choroidal neovascularization. Invest Ophthalmol Vis Sci 2002; 43: 1994-2000
    PubMedGoogle Scholar
  • 25 Chen P, Hamilton M, Thomas CA et al. Persistent expression of PEDF in the eye using high-capacity adenovectors. Mol Ther 2008; 16: 1986-1994
    CrossrefPubMedGoogle Scholar
  • 26 Kim JH, Kim MH, Jo DH et al. The inhibition of retinal neovascularization by gold nanoparticles via suppression of vegfr-2 activation. Biomaterials 2011; 32: 1865-1871
    CrossrefPubMedGoogle Scholar
  • 27 Kalishwaralal K, Barathmanikanth S, Pandian SR et al. Silver nano – a trove for retinal therapies. J Control Release 2010; 145: 76-90
    CrossrefPubMedGoogle Scholar
  • 28 Jo DH, Kim JH, Yu YS et al. Antiangiogenic effect of silicate nanoparticle on retinal neovascularization induced by vascular endothelial growth factor. Nanomedicine 2011; Sep 21 [Epub ahead of print]
    PubMedGoogle Scholar
  • 29 Bainbridge JWB, Smith AJ, Barker SS et al. Effect of gene therapy on visual function in Leber’s congenital amaurosis. N Engl J Med 2008; 358: 2231-2239
    CrossrefPubMedGoogle Scholar
  • 30 Acland GM, Aguirre GD, Ray J et al. Gene therapy restores vision in a canine model of childhood blindness. Nat Genet 2001; 28: 92-95
    PubMedGoogle Scholar
  • 31 Narfström K, Katz ML, Bragadottir R et al. Functional and structural recovery of the retina after gene therapy in the RPE65 null mutation dog. Invest Ophthalmol Vis Sci 2003; 44: 1663-1672
    CrossrefPubMedGoogle Scholar
  • 32 Cideciyan AV, Aleman TS, Boye SL et al. Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proc Natl Acad Sci USA 2008; 105: 15112-15117
    CrossrefPubMedGoogle Scholar
  • 33 Jacobson SG, Aleman TS, Cideciyan AV et al. Identifying photoreceptors in blind eyes caused by RPE65 mutations: Prerequisite for human gene therapy success. Proc Natl Acad Sci USA 2005; 102: 6177-6182
    CrossrefPubMedGoogle Scholar
  • 34 Tschernutter M, Schlichtenbrede FC, Howe S et al. Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy. Gene Ther 2005; 12: 694-701
    CrossrefPubMedGoogle Scholar
  • 35 Sakai T, Kohno H, Ishihara T et al. Treatment of experimental autoimmune uveoretinitis with poly(lactic acid) nanoparticles encapsulating betamethasone phosphate. Exp Eye Res 2006; 82: 657-663
    CrossrefPubMedGoogle Scholar
  • 36 de Kozak Y, Andrieux K, Villarroya H et al. Intraocular injection of tamoxifen-loaded nanoparticles: A new treatment of experimental autoimmune uveoretinitis. Eur J Immunol 2004; 34: 3702-3712
    CrossrefPubMedGoogle Scholar
  • 37 Martin KRG, Quigley HA, Zack DJ et al. Gene therapy with brain-derived neurotrophic factor as a protection: retinal ganglion cells in a rat glaucoma model. Invest Ophthalmol Vis Sci 2003; 44: 4357-4365
    CrossrefPubMedGoogle Scholar
  • 38 Sullivan TA, Geisert EE, Hines-Beard J et al. Systemic adeno-associated virus-mediated gene therapy preserves retinal ganglion cells and visual function in DBA/2J glaucomatous mice. Hum Gene Ther 2011; 22: 1191-1200
    CrossrefPubMedGoogle Scholar
  • 39 Buss DG, Giuliano E, Sharma A et al. Gene delivery in the equine cornea: a novel therapeutic strategy. Vet Ophthalmol 2010; 13: 301-306
    CrossrefPubMedGoogle Scholar
  • 40 Mohan RR, Tovey JC, Gupta R et al. Decorin biology, expression, function and therapy in the cornea. Curr Mol Med 2011; 11: 110-128
    CrossrefPubMedGoogle Scholar
  • 41 Mohan RR, Tovey JC, Sharma A et al. Targeted decorin gene therapy delivered with adeno-associated virus effectively retards corneal neovascularization in vivo. PLoS One 2011; 6: e26432
    CrossrefPubMedGoogle Scholar