nach oben

Die Ophthalmologie

Erschienen in:

01.07.2005 | Leitthema

Stammzellbasierte Therapieansätze für retinale Erkrankungen

verfasst von: PD Dr. U. Bartsch, S. J. Linke, B. Petrowitz

Erschienen in: Die Ophthalmologie | Ausgabe 7/2005

Einloggen, um Zugang zu erhalten

Zusammenfassung

Im Rahmen zellbasierter Therapien für erbliche Netzhautdystrophien und verschiedene andere retinale Erkrankungen hat sich das Interesse zunehmend auf die therapeutischen Anwendungsmöglichkeiten von embryonalen und gewebespezifischen Stammzellen fokussiert. Stammzellen sind durch ihre Fähigkeit zur Selbsterneuerung und ihre Multipotenz charakterisiert. Aufgrund dieser Eigenschaften können sie in vitro vermehrt und potenziell in ganz bestimmte, „erwünschte“ Zelltypen differenziert werden. Stammzellen sind nicht nur Kandidatenzellen für die Entwicklung von Zellersatzstrategien, sondern auch interessante Zellen für den Aufbau von ex-vivo-Gentherapien. In diesem Artikel werden Experimente diskutiert, in denen das zelltherapeutische Potenzial von embryonalen, mesenchymalen, hämatopoetischen, neuralen und retinalen Stammzellen für die Behandlung hereditärer Netzhautdystrophien und verschiedener anderer retinaler Erkrankungen untersucht wurde.

Acland GM, Aguirre GD, Ray J et al. (2001) Gene therapy restores vision in a canine model of childhood blindness. Nat Genet 28:92–95PubMed

Ader M, Meng J, Schachner M, Bartsch U (2000) Formation of myelin after transplantation of neural precursor cells into the retina of young postnatal mice. Glia 30:301–310CrossRefPubMed

Ahmad I (2001) Stem cells: new opportunities to treat eye diseases. Invest Ophthalmol Vis Sci 42:2743–2748PubMed

Ahmad I, Tang L, Pham H (2000) Iden.jpgication of neural progenitors in the adult mammalian eye. Biochem Biophys Res Com 270:517–521CrossRefPubMed

Ali RR, Sarra GM, Stephens C et al. (2000) Restoration of photoreceptor ultrastructure and function in retinal degeneration slow mice by gene therapy. Nat Genet 25:306–310CrossRefPubMed

Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM et al. (2003) Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425:968–973CrossRefPubMed

Anderson DJ, Gage FH, Weissman IL (2001) Can stem cells cross lineage boundaries? Nat Med 7:393–395CrossRefPubMed

Bartsch U, Richard G, Linke S (2003) Stammzell-Therapie in der Ophthalmologie. medgen 15:167–172

Bennett J, Zeng Y, Bajwa R, Klatt L, Li Y, Maguire AM (1998) Adenovirus-mediated delivery of rhodopsin-promoted bcl-2 results in a delay in photoreceptor cell death in the rd/rd mouse. Gene Ther 5:1156–1164CrossRefPubMed

10.

Brüstle O, Jones KN, Learish RD et al. (1999) Embryonic stem-cell derived glial precursors: a source of myelinating transplants. Science 285:754–756CrossRefPubMed

11.

Cao Q, Benton RL, Whittemore SR (2002) Stem cell repair of central nervous system injury. J Neurosci Res 68:501–510CrossRefPubMed

12.

Cayouette M, Behn D, Sendtner M, Lachapelle P, Gravel C (1998) Intraocular gene transfer of ciliary neurotrophic factor prevents death and increases responsiveness of rod photoreceptors in the retinal degeneration slow mouse. J Neurosci 18:9282–9293PubMed

13.

Chacko DM, Das AV, Zhao X, James J, Bhattacharya S, Ahmad I (2003) Transplantation of ocular stem cells: the role of injury in incorporation and differentiation of grafted cells in the retina. Vis Res 43:937–946CrossRefPubMed

14.

Chen J, Flannery JG, LaVail MM, Steinberg RH, Xu J, Simon MI (1996) bcl-2 overexpression reduces apoptotic photoreceptor cell death in three different retinal degenerations. Proc Natl Acad Sci USA 93:7042–7047CrossRefPubMedPubMedCentral

15.

Coles BL, Angenieux B, Inoue T et al. (2004) Facile isolation and the characterization of human retinal stem cells. Proc Natl Acad Sci USA 101:15772–15777CrossRefPubMedPubMedCentral

16.

Dong X, Pulido JS, Qu T, Sugaya K (2003) Differentiation of human neural stem cells into retinal cells. NeuroReport 14:143–146CrossRefPubMed

17.

Gage FH (2000) Mammalian neural stem cells. Science 287:1433–1438CrossRefPubMed

18.

Galli R, Gritti A, Bonfanti L, Vescovi AL (2003) Neural stem cells: An overview. Circ Res 92:598–608CrossRefPubMed

19.

Glaser T, Perez-Bouza A, Klein K, Brüstle O (2004) Generation of purified oligodendrocyte progenitors from embryonic stem cells. FASEB J (in press)

20.

Gouras P, Kong J, Tsang SH (2002) Retinal degeneration and RPE transplantation in Rpe65 (-/-) mice. Invest Ophthalmol Vis Sci 43:3307–3311PubMed

21.

Haruta M, Sasai Y, Kawasaki H et al. (2004) In vitro and in vivo characterization of pigment epithelial cells differentiated from primate embryonic stem cells. Invest Ophthalmol Vis Sci 45:1020–1025CrossRefPubMed

22.

Kawasaki H, Suemori H, Mizuseki K et al. (2002) Generation of dopaminergic neurons and pigmented epithelia from primate ES cells by stromal cell-derived inducing activity. Proc Natl Acad Sci USA 99:1580–1585CrossRefPubMedPubMedCentral

23.

Kehat I, Khimovich L, Caspi O et al. (2004) Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol 22:1282–1289CrossRefPubMed

24.

Kicic A, Shen WY, Wilson AS, Constable IJ, Robertson T, Rakoczy PE (2003) Differentiation of marrow stromal cells into photoreceptors in the rat eye. J Neurosci 23:7742–7749PubMed

25.

Kim JH, Auerbach JM, Rodriguez-Gomez JA et al. (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature 418:50–56CrossRefPubMed

26.

Klug MG, Soonpaa MH, Koh GY, Field LJ (1996) Genetically selected cardiomyocytes from differentiating embryonic stem cells form stable intracardiac grafts. J Clin Invest 98:216–224CrossRefPubMedPubMedCentral

27.

Kurimoto Y, Shibuki H, Kaneko Y, Ichikawa M, Kurokawa T, Takahashi M, Yoshimura N (2001) Transplantation of adult rat hippocampus-derived neural stem cells into retina injured by transient ischemia. Neurosci Lett 306:57–60CrossRefPubMed

28.

LaVail MM, Yasumura D, Matthes MT, Lau-Villacorta C, Unoki K, Sung CH, Steinberg RH (1998) Protection of mouse photoreceptors by survival factors in retinal degenerations. Invest Ophthalmol Vis Sci 39:592–602PubMed

29.

LaVail MM, Yasumura D, Matthes MT, Drenser KA, Flannery JG, Lewin AS, Hauswirth WW (2000) Ribozyme rescue of photoreceptor cells in P23H transgenic rats: long-term survival and late-stage therapy. Proc Natl Acad Sci USA 97:11488–11493CrossRefPubMedPubMedCentral

30.

Lewin AS, Drenser KA, Hauswirth WW, Nishikawa S, Yasumura D, Flannery JG, LaVail MM (1998) Ribozyme rescue of photoreceptor cells in a transgenic rat model of autosomal dominant retinitis pigmentosa. Nat Med 4:967–971CrossRefPubMed

31.

Lindvall O, Kokaia Z, Martinez-Serrano A (2004) Stem cell therapy for human neurodegenerative disorders — how to make it work. Nat Med 10:42–50CrossRef

32.

Lu B, Kwan T, Kurimoto Y, Shatos M, Lund RD, Young MJ (2002) Transplantation of EGF-responsive neurospheres from GFP transgenic mice into the eyes of rd mice. Brain Res 943:292–300CrossRefPubMed

33.

Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, McKay R (2001) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292:1389–1394CrossRefPubMed

34.

Lund RD, Kwan AS, Keegan DJ, Sauve Y, Coffey PJ, Lawrence JM (2001) Cell transplantation as a treatment for retinal disease. Prog Ret Eye Res 20:415–449CrossRef

35.

Lund RD, Ono SJ, Keegan DJ, Lawrence JM (2003) Retinal transplantation: progress and problems in clinical applications. J Leukoc Biol 74:151–160CrossRefPubMed

36.

McKay R (1997) Stem cells in the central nervous system. Science 276:66–71CrossRefPubMed

37.

Mellough CB, Cui Q, Spalding KL et al. (2004) Fate of multipotent neural precursor cells transplanted into mouse retina selectively depleted of retinal ganglion cells. Exp Neurol 186:6–19CrossRefPubMed

38.

Meyer JS, Katz ML, Maruniak JA, Kirk MD (2004) Neural differentiation of mouse embryonic stem cells in vitro and after transplantation into eyes of mutant mice with rapid retinal degeneration. Brain Res 1014:131–144CrossRefPubMed

39.

Mizumoto H, Mizumoto K, Whiteley SJ, Shatos M, Klassen H, Young MJ (2001) Transplantation of human neural progenitor cells to the vitreous cavity of the Royal College of Surgeons rat. Cell Transplant 10:223–233PubMed

40.

Morrison SJ (2001) Stem cell potential: can anything make anything? Curr Biol 11:7–9CrossRef

41.

Nishida A, Takahashi M, Tanihara H et al. (2000) Incorporation and differentiation of hippocampus-derived neural stem cells transplanted in injured adult rat retina. Invest Ophthalmol Vis Sci 41:4268–4274PubMed

42.

Otani A, Kinder K, Ewalt K, Otero FJ, Schimmel P, Friedlander M (2002) Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis. Nat Med 8:1004–1010CrossRefPubMed

43.

Otani A, Dorrell MI, Kinder K et al. (2004) Rescue of retinal degeneration by intravitreally injected adult bone marrow-derived lineage-negative hematopoietic stem cells. J Clin Invest 114:765–774CrossRefPubMedPubMedCentral

44.

Perrier AL, Tabar V, Barberi T et al. (2004) Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc Natl Acad Sci U S A 101:12543–12548CrossRefPubMedPubMedCentral

45.

Pressmar S, Ader M, Richard G, Schachner M, Bartsch U (2001) The fate of heterotopically grafted neural precursor cells in the normal and dystrophic adult mouse retina. Invest Ophthalmol Vis Sci 42:3311–3319PubMed

46.

Raff M (2003) Adult stem cell plasticity: fact or ar.jpgact? Annu Rev Cell Dev Biol 19:1–22CrossRefPubMed

47.

Sakaguchi DS, van Hoffelen SJ, Young MJ (2003) Differentiation and morphological integration of neural progenitor cells transplanted into the developing mammalian eye. Ann NY Acad Sci 995:127–139CrossRefPubMed

48.

Sauve Y, Girman SV, Wang S, Keegan DJ, Lund RD (2002) Preservation of visual responsiveness in the superior colliculus of RCS rats after retinal pigment epithelium cell transplantation. Neuroscience 114:389–401CrossRefPubMed

49.

Schraermeyer U, Thumann G, Luther T et al. (2001) Subretinally transplanted embryonic stem cells rescue photoreceptor cells from degeneration in the RCS rats. Cell Transpl 10:673–680

50.

Soria B, Roche E, Berna G, Leon-Quinto T, Reig JA, Martin F (2000) Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 49:157–162CrossRefPubMed

51.

Svendsen CN, Caldwell MA (2000) Neural stem cells in the developing central nervous system: implications for cell therapy through transplantation. Prog Brain Res 127:13–34CrossRefPubMed

52.

Tabata Y, Ouchi Y, Kamiya H, Manabe T, Arai KI, Watanabe S (2004) Specification of the retinal fate of mouse embryonic stem cells by ectopic expression of Rx/rax, a homeobox gene. Mol Cell Biol 24:4513–4521CrossRefPubMedPubMedCentral

53.

Takahashi M, Palmer TD, Takahashi J, Gage FH (1998) Widespread integration and survival of adult-derived neural progenitor cells in the developing optic retina. Mol Cell Neurosci 12:340–348CrossRefPubMed

54.

Tomita M, Adachi Y, Yamada H et al. (2002) Bone marrow-derived stem cells can differentiate into retinal cells in injured rat retina. Stem Cells 20:279–283CrossRefPubMed

55.

Tropepe V, Coles BL, Chiasson BJ, Horsford DJ, Elia AJ, McInnes RR, van der Kooy D (2000) Retinal stem cells in the adult mammalian eye. Science 287:2032–2036CrossRefPubMed

56.

Van Hoffelen SJ, Young MJ, Shatos MA, Sakaguchi DS (2003) Incorporation of murine brain progenitor cells into the developing mammalian retina. Invest Ophthalmol Vis Sci 44:426–434CrossRefPubMed

57.

Vollrath D, Feng W, Duncan JL et al. (2001) Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk. Proc Natl Acad Sci USA 98:12584–12589CrossRefPubMedPubMedCentral

58.

Wichterle H, Lieberam I, Porter JA, Jessell TM (2002) Directed differentiation of embryonic stem cells into motor neurons. Cell 110:385–397CrossRefPubMed

59.

Wojciechowski AB, Englund U, Lundberg C, Wictorin K, Warfvinge K (2002a) Subretinal transplantation of brain-derived precursor cells to young RCS rats promotes photoreceptor cell survival. Exp Eye Res 75:23–37CrossRefPubMed

60.

Wojciechowski AB, Englund U, Lundberg C, Warfvinge K (2002b) Long-term survival and glial differentiation of the brain-derived precursor cell line RN33B after subretinal transplantation to adult normal rats. Stem cells 20:163–173CrossRefPubMed

61.

Wurmser AE, Gage FH (2002) Stem cells: cell fusion causes confusion. Nature 416:485–487CrossRefPubMed

62.

Young MJ, Ray J, Whiteley SJ, Klassen H, Gage FH (2000) Neuronal differentiation and morphological integration of hippocampal progenitor cells transplanted to the retina of immature and mature dystrophic rats. Mol Cell Neurosci 16:197–205CrossRefPubMed

63.

Zhao X, Liu J, Ahmad I (2002) Differentiation of embryonic stem cells into retinal neurons. Biochem Biophys Res Com 297:177–184CrossRefPubMed

64.

Zrenner E (2002) Will retinal implants restore vision? Science 295:1022–1025CrossRefPubMed

Titel: Stammzellbasierte Therapieansätze für retinale Erkrankungen
verfasst von: PD Dr. U. Bartsch
S. J. Linke
B. Petrowitz
Publikationsdatum: 01.07.2005
Verlag: Springer Berlin Heidelberg
Erschienen in: Die Ophthalmologie / Ausgabe 7/2005
Print ISSN: 2731-720X
Elektronische ISSN: 2731-7218
DOI: https://doi.org/10.1007/s00347-005-1188-4

Neu im Fachgebiet Augenheilkunde

08.04.2024 | Therapieverfahren in der Augenheilkunde | CME

Update Augenheilkunde

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Stammzellbasierte Therapieansätze für retinale Erkrankungen

Zusammenfassung

Neu im Fachgebiet Augenheilkunde

Ophthalmika in der Schwangerschaft

Operative Therapie und Keimnachweis bei endogener Endophthalmitis

Bakterielle endogene Endophthalmitis

So erreichen Sie eine bestmögliche Wundheilung der Kornea

Update Augenheilkunde

Springer Medizin

Zusammenfassung

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 7/2005

Therapeutische Strategien bei erblichen Netzhauterkrankungen

Einfluss von Kantenfiltern auf die Lesefähigkeit bei altersabhängiger Makuladegeneration

„Haben Sie ein Mittel gegen Makuladegeneration?“

Akute, monokulare Visusreduktion bei schwangerer Patientin

Symptomatische Harntransportstörung nach malignem Melanom der Aderhaut

Programmierter Zelltod in der Netzhaut

Neu im Fachgebiet Augenheilkunde

Ophthalmika in der Schwangerschaft

Operative Therapie und Keimnachweis bei endogener Endophthalmitis

Bakterielle endogene Endophthalmitis

So erreichen Sie eine bestmögliche Wundheilung der Kornea

Update Augenheilkunde