Survey of Ophthalmology
Volume 47, Issue 5 , Pages 449-469 , September 2002

Gene Therapy for Genetic and Acquired Retinal Diseases

  • Edward Chaum, MD, PhD

      Affiliations

    • Corresponding Author InformationReprint address: Edward Chaum, MD PhD, Department of Ophthalmology, University of Tennessee Health Science Center, 956 Court Ave. Rm D228, Memphis, TN
    • Departments of Ophthalmology, Pediatrics, Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN USA
    • ,
  • Mark P Hatton, MD

      Affiliations

    • Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachussetts, USA

References 

  1. Abdallah B, Hassan A, Benoist C, et al.  A powerful nonviral vector for in vivo gene transfer into the adult mammalian brain (polyethylenimine). Hum Gene Ther. 1996;7:1947–1954
  2. Abraham NG, da Silva JL, Lavrovsky Y, et al.  Adenovirus-mediated heme oxygenase-1 gene transfer into rabbit ocular tissues. Invest Ophthalmol Vis Sci. 1995;36:2202–2210
  3. 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
  4. Adler R. Mechanisms of photoreceptor death in retinal degenerations. From the cell biology of the. 1996;1990s(to the ophthalmology of the 21st century? Arch Ophthalmol 114):79–83
  5. Aguirre GD, Baldwin V, Pearce-Kelling S, et al.  Congenital stationary night blindness in the dog (common mutation in the RPE65 gene indicates founder effect). Mol Vis. 1998;4:23
  6. Akimoto M, Miyatake S, Kogishi J, et al.  Adenovirally expressed basic fibroblast growth factor rescues photoreceptor cells in RCS rats. Invest Ophthalmol Vis Sci. 1999;40:273–279
  7. Ali RR, Reichel MB, Thrasher AJ, et al.  Gene transfer into the mouse retina mediated by an adeno-associated viral vector. Hum Mol Genet. 1996;5:591–594
  8. Ali RR, Sarra GM, Stephens C, et al.  Restoration of photoreceptor ultrastructure and function in retinal degeneration slow mice by gene therapy. Nat Genet. 2000;25:306–310
  9. Allikmets R, Shroyer NF, Singh N, et al.  Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science. 1997;277:1805–1807
  10. Allsopp TE, Wyatt S, Paterson HF, Davies AM. The proto-oncogene bcl-2 can selectively rescue neurotrophic factor- dependent neurons from apoptosis. Cell. 1993;73:295–307
  11. Anand V, Chirmule N, Fersh M, et al.  Additional transduction events after subretinal readministration of recombinant adeno-associated virus. Hum Gene Ther. 2000;11:449–457
  12. Andrews A, Balciunaite E, Leong FL, et al.  Platelet-derived growth factor plays a key role in proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci. 1999;40:2683–2689
  13. Anglade E, Csaky KG. Recombinant adenovirus-mediated gene transfer into the adult rat retina. Curr Eye Res. 1998;17:316–321
  14. Ash JD, Rapp LM, Overbeek PA. Photoreceptor development is blocked by the lens-specific expression of leukemia inhibitory factor (LIF). Invest Ophthalmol Vis Sci. 1997;38(Suppl):S226; [abstract]
  15. Bebok Z, Abai AM, Dong JY, et al.  Efficiency of plasmid delivery and expression after lipid-mediated gene transfer to human cells in vitro. J Pharmacol Exp Ther. 1996;279:1462–1469
  16. Behr JP, Demeneix B, Loeffler JP, Perez-Mutul J. Efficient gene transfer into mammalian primary endocrine cells with lipopolyamine-coated DNA. Proc Natl Acad Sci USA. 1989;86:6982–6986
  17. Bell WJ, O-Rourke P, Budz V. Sustained delivery of hCNTF to rabbit vitreous humor by encapsulated cell technology. Invest Ophthalmol Vis Sci. 2001;42:S171; [abstract]
  18. Bennett J: Retinal gene therapy in the 21st century. The Fourth Great Basin Visual Science Symposium, August 18, 2000. (Available at http://insight.med.utah.edu/gbs/gbs4/ pdf/bennett_paper.pdf)
  19. Bennett J, Duan D, Engelhardt JF, Maguire AM. Real-time, noninvasive in vivo assessment of adeno-associated virus- mediated retinal transduction. Invest Ophthalmol Vis Sci. 1997;38:2857–2863
  20. Bennett J, Maguire AM. Gene therapy for ocular disease. Mol Ther. 2000;1:501–505
  21. Bennett J, Maguire AM: Gene therapy, in Berger JW, Fine SL, Maguire MG (eds): Age-Related Macular Degeneration. St Louis, Mosby, 1999 pp 395–412
  22. Bennett J, Maguire AM, Cideciyan AV, et al.  Stable transgene expression in rod photoreceptors after recombinant adeno-associated virus-mediated gene transfer to monkey retina. Proc Natl Acad Sci USA. 1999;96:9920–9925
  23. Bennett J, Pakola S, Zeng Y, Maguire A. Humoral response after administration of E1-deleted adenoviruses (immune privilege of the subretinal space). Hum Gene Ther. 1996;7:1763–1769
  24. Bennett J, Tanabe T, Sun D, et al.  Photoreceptor cell rescue in retinal degeneration (rd) mice by in vivo gene therapy. Nat Med. 1996;2:649–654
  25. Bennett J, Wilson J, Sun D, et al.  Adenovirus vector-mediated in vivo gene transfer into adult murine retina. Invest Ophthalmol Vis Sci. 1994;35:2535–2542
  26. Bennett J, Zeng Y, Bajwa R, et al.  Adenovirus-mediated delivery of rhodopsin-promoted bcl-2 results in a delay in photoreceptor cell death in the rd/rd mouse. Gene Ther. 1998;5:1156–1164
  27. Bessant DA, Ali RR, Bhattacharya SS. Molecular genetics and prospects for therapy of the inherited retinal dystrophies. Curr Opin Genet Dev. 2001;11:307–316
  28. Bi WL, Parysek LM, Warnick R, Stambrook PJ. In vitro evidence that metabolic cooperation is responsible for the bystander effect observed with HSV tk retroviral gene therapy. Hum Gene Ther. 1993;4:725–731
  29. Birikh KR, Heaton PA, Eckstein F. The structure, function and application of the hammerhead ribozyme. Eur J Biochem. 1997;245:1–16
  30. Blanks JC. Gene therapy for photoreceptor degeneration, in Quiroz-Mercado H, Liggett P, Alfaro V, et al (eds): Macular Surgery. New York, Lippincott, Williams and Wilkins, 2000, pp 260–74
  31. Borras T, Matsumoto Y, Epstein DL, Johnson DH. Gene transfer to the human trabecular meshwork by anterior segment perfusion. Invest Ophthalmol Vis Sci. 1998;39:1503–1507
  32. Borras T, Tamm ER, Zigler JS. Ocular adenovirus gene transfer varies in efficiency and inflammatory response. Invest Ophthalmol Vis Sci. 1996;37:1282–1293
  33. Bradshaw JJ, Obritsch WF, Cho BJ, et al.  Ex vivo transduction of corneal epithelial progenitor cells using a retroviral vector. Invest Ophthalmol Vis Sci. 1999;40:230–235
  34. Brandt CR, Kintner RL, Pumfery AM, et al.  The herpes simplex virus ribonucleotide reductase is required for ocular virulence. J Gen Virol. 1991;72:2043–2049
  35. Breakefield XO, DeLuca NA. Herpes simplex virus for gene delivery to neurons. New Biol. 1991;3:203–218
  36. Calabretta B, Skorski T, Ratajczak MZ, Gewirtz AM. Antisense strategies in the treatment of leukemias. Semin Oncol. 1996;23:78–87
  37. Campochiaro PA, Hackett SF, Vinores SA, et al.  Platelet-derived growth factor is an autocrine growth stimulator in retinal pigmented epithelial cells. J Cell Sci. 1994;107:2459–2469
  38. Capeans C, Pineiro A, Dominguez F, et al.  A c-myc antisense oligonucleotide inhibits human retinal pigment epithelial cell proliferation. Exp Eye Res. 1998;66:581–589
  39. Caplen NJ, Kinrade E, Sorgi F, et al.  In vitro liposome-mediated DNA transfection of epithelial cell lines using the cationic liposome DC-Chol/DOPE. Gene Ther. 1995;2:603–613
  40. Carter BJ. Adeno-associated virus vectors. Curr Opin Biotechnol. 1992;3:533–539
  41. Cavenee WK, Dryja TP, Phillips RA, et al.  Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature. 1983;305:779–784
  42. Cayouette M, Behn D, Sendtner M, et al.  Intraocular gene transfer of ciliary neurotrophic factor prevents death and increases responsiveness of rod photoreceptors in the retinal degeneration slow mouse. J Neurosci. 1998;18:9282–9293
  43. Cayouette M, Gravel C. Adenovirus-mediated gene transfer of ciliary neurotrophic factor can prevent photoreceptor degeneration in the retinal degeneration (rd) mouse. Hum Gene Ther. 1997;8:423–430
  44. Cayouette M, Gravel C. Adenovirus-mediated gene transfer to retinal ganglion cells. Invest Ophthalmol Vis Sci. 1996;37:2022–2028
  45. Chang MA, Horner JW, Conklin BR, et al.  Tetracycline-inducible system for photoreceptor-specific gene expression. Invest Ophthalmol Vis Sci. 2000;41:4281–4287
  46. Chaum E. Comparative analysis of the uptake and expression of plasmid vectors in human ciliary and retinal pigment epithelial cells in vitro. J Cell Biochem. 2001;83:671–677
  47. Chaum E. Proliferative vitreoretinopathy. Int Ophthalmol Clin. 1995;35:163–173
  48. Chaum E, Hatton MP, Stein G. Polyplex-mediated gene transfer into human retinal pigment epithelial cells in vitro. J Cell Biochem. 1999;76:153–160
  49. Chaum E, Holleck J. Polyplex-mediated gene transfer and expression of insulin-like growth factor-1 in human retinal pigment epithelial cells (phenotypic response to IGF-1 transgene expression in vitro). Invest Ophthalmol Vis Sci. 1999;40(Suppl):S716; [abstract]
  50. Chen J, Flannery JG, LaVail MM, et al.  bcl-2 overexpression reduces apoptotic photoreceptor cell death in three different retinal degenerations. Proc Natl Acad Sci USA. 1996;93:7042–7047
  51. Chowers I, Banin E, Hemo Y, et al.  Gene transfer by viral vectors into blood vessels in a rat model of retinopathy of prematurity. Br J Ophthalmol. 2001;85:991–995
  52. Clements PJ, Gregory CY, Peterson-Jones SM, et al.  Confirmation of the rod cGMP phosphodiesterase beta subunit (PDE beta) nonsense mutation in affected rcd-1 Irish setters in the UK and development of a diagnostic test. Curr Eye Res. 1993;12:861–866
  53. Couderc BC, de Neuville S, Douin-Echinard V, et al.  Retrovirus-mediated transfer of a suicide gene into lens epithelial cells in vitro and in an experimental model of posterior capsule opacification. Curr Eye Res. 1999;19:472–482
  54. Culver KW. Gene therapy for malignant neoplasms of the CNS. Bone Marrow Transplant. 1996;18(Suppl 3):S6–S9
  55. da Cruz L, Rakoczy P, Perricaudet M, Constable IJ. Dynamics of gene transfer to retinal pigment epithelium. Invest Ophthalmol Vis Sci. 1996;37:2447–2454
  56. da Cruz L, Robertson T, Hall MO, et al.  Cell polarity, phagocytosis and viral gene transfer in cultured human retinal pigment epithelial cells. Curr Eye Res. 1998;17:668–672
  57. Daly TM, Ohlemiller KK, Roberts MS, et al.  Prevention of systemic clinical disease in MPS VII mice following AAV-mediated neonatal gene transfer. Gene Ther. 2001;8:1291–1298
  58. Daly TM, Vogler C, Levy B, et al.  Neonatal gene transfer leads to widespread correction of pathology in a murine model of lysosomal storage disease. Proc Natl Acad Sci USA. 1999;96:2296–2300
  59. De Bizemont TJ, Berdugo M, Courtois Y. Confocale laser scanning microscopy of the anterior segment of the rat and mouse eye after iontophoresis of fluorescent antisense oligonucleotides. Invest Ophthalmol Vis Sci. 2001;42(Suppl):S171; [abstract]
  60. Dejneka NS, Auricchio A, Maguire AM, et al.  Pharmacologically regulated gene expression in the retina following transduction with viral vectors. Gene Ther. 2001;8:442–446
  61. Dezawa M, Takano M, Negishi H, et al.  Gene transfer into retinal ganglion cells by in vivo electroporation (a new approach). Micron. 2002;33:1–6
  62. Di Polo A, Aigner LJ, Dunn RJ, et al.  Prolonged delivery of brain-derived neurotrophic factor by adenovirus-infected Muller cells temporarily rescues injured retinal ganglion cells. Proc Natl Acad Sci USA. 1998;95:3978–3983
  63. Drenser KA, Timmers AM, Hauswirth WW, Lewin AS. Ribozyme-targeted destruction of RNA associated with autosomal-dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci. 1998;39:681–689
  64. Dryja TP, Cavenee W, White R, et al.  Homozygosity of chromosome 13 in retinoblastoma. N Engl J Med. 1984;310:550–553
  65. Elion GB, Furman PA, Fyfe JA. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine. Proc Natl Acad Sci USA. 1977;74:5716–5720
  66. Faktorovich EG, Steinberg RH, Yasumura D, et al.  Photoreceptor degeneration in inherited retinal dystrophy delayed by basic fibroblast growth factor. Nature. 1990;347:83–86
  67. Faktorovitch EG, Steinberg RH, Yasumura D. Basic fibroblast growth factor and local injury protect photoreceptors from light damage in the rat. J Neurosci. 1992;12:3554–3567
  68. Fehervari Z, Rayner SA, Oral HB, et al.  Gene transfer to ex vivo stored corneas. Cornea. 1997;16:459–464
  69. Felgner PL, Gadek TR, Holm M, et al.  Lipofection (a highly efficient, lipid-mediated DNA-transfection procedure). Proc Natl Acad Sci USA. 1987;84:7413–7417
  70. Felgner PL, Ringold GM. Cationic liposome-mediated transfection. Nature. 1989;337:387–388
  71. Flannery JG, Zolotukhin S, Vaquero MI, et al.  Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus. Proc Natl Acad Sci USA. 1997;94:6916–6921
  72. Frasson M, Picaud S, Leveillard T, et al.  Glial cell line-derived neurotrophic factor induces histologic and functional protection of rod photoreceptors in the rd/rd mouse. Invest Ophthalmol Vis Sci. 1999;40:2724–2734
  73. Freeman SM, Abboud CN, Whartenby KA, et al.  The bystander effect (tumor regression when a fraction of the tumor mass is genetically modified). Cancer Res. 1993;53:5274–5283
  74. Friend DS, Papahadjopoulos D, Debs RJ. Endocytosis and intracellular processing accompanying transfection mediated by cationic liposomes. Biochim Biophys Acta. 1996;1278:41–50
  75. Fukuhara M, Suzuki A, Fukuda Y, Kosaka J. Adenovirus vector-mediated gene transfer into rat retinal neurons and Muller cells in vitro and in vivo. Neurosci Lett. 1998;242:93–96
  76. Galileo DS, Hunter K, Smith SB. Stable and efficient gene transfer into the mutant retinal pigment epithelial cells of the Mitf(vit) mouse using a lentiviral vector. Curr Eye Res. 1999;18:135–142
  77. Garcia Valenzuela E, Sharma SC. Rescue of retinal ganglion cells from axotomy-induced apoptosis through TRK oncogene transfer. Neuroreport. 1998;9:3165–3170
  78. Gershon H, Ghirlando R, Guttman SB, Minsky A. Mode of formation and structural features of DNA-cationic liposome complexes used for transfection. Biochemistry. 1993;32:7143–7151
  79. Glaser BM, Lemor M. Pathobiology of proliferative vitreoretinopathy. In:  Ryan SJ editors. Retina, Vol. 3. St Louis: Mosby; 1998;p. 369–383
  80. Graham FL, van der Eb AJ. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973;52:456–467
  81. Grant CA, Ponnazhagan S, Wang XS, et al.  Evaluation of recombinant adeno-associated virus as a gene transfer vector for the retina. Curr Eye Res. 1997;16:949–956
  82. Grether ME, Abrams JM, Agapite J, et al.  The head involution defective gene of Drosophila melanogaster functions in programmed cell death. Genes Dev. 1995;9:1694–1708
  83. Gupta SK, Jollimore CA, McLaren MJ, et al.  Mammalian retinal pigment epithelial cells in vitro respond to the neurokines ciliary neurotrophic factor and leukemia inhibitory factor. Biochem Cell Biol. 1997;75:119–125
  84. Guy J, Qi X, Muzyczka N. Reporter expression persists 1 year after adeno-associated virus-mediated gene transfer to the optic nerve. Arch Ophthalmol. 1999;117:929–937
  85. Haeseleer F, Imanishi Y, Saperstein DA, Palczewski K. Gene transfer mediated by recombinant baculovirus into mouse eye. Invest Ophthalmol Vis Sci. 2001;42:3294–3300
  86. Hangai M, Kaneda Y, Tanihara H, Honda Y. In vivo gene transfer into the retina mediated by a novel liposome system. Invest Ophthalmol Vis Sci. 1996;37:2678–2685
  87. Hangai M, Tanihara H, Honda Y, Kaneda Y. Introduction of DNA into the rat and primate trabecular meshwork by fusogenic liposomes. Invest Ophthalmol Vis Sci. 1998;39:509–516
  88. Haseloff J, Gerlach WL. Simple RNA enzymes with new and highly specific endoribonuclease activities. Nature. 1988;334:585–591
  89. Hauswirth WW, Beaufrere L. Ocular gene therapy (quo vadis?). Invest Ophthalmol Vis Sci. 2000;41:2821–2826
  90. Hauswirth WW, LaVail MM, Flannery JG, Lewin AS. Ribozyme gene therapy for autosomal dominant retinal disease. Clin Chem Lab Med. 2000;38:147–153
  91. Hauswirth WW, McInnes RR. Retinal gene therapy 1998 (summary of a workshop). Mol Vis. 1998;4:11; Available at http://www.molvis.org/molvis/v4/p11
  92. Hauswirth WW, Timmers AM. The eyes have it. Mol Med Today. 2000;6:51
  93. Hayashi N, Ido E, Ohtsuki Y, Ueno H. An experimental application of gene therapy for human retinoblastoma. Invest Ophthalmol Vis Sci. 1999;40:265–272
  94. Hoffman LM, Maguire AM, Bennett J. Cell-mediated immune response and stability of intraocular transgene expression after adenovirus-mediated delivery. Invest Ophthalmol Vis Sci. 1997;38:2224–2233
  95. Huang HJ, Yee JK, Shew JY, et al.  Suppression of the neoplastic phenotype by replacement of the RB gene in human cancer cells. Science. 1988;242:1563–1566
  96. Humphries MM, Rancourt D, Farrar GJ, et al.  Retinopathy induced in mice by targeted disruption of the rhodopsin gene. Nat Genet. 1997;15:216–219
  97. Hurwitz MY, Marcus KT, Chevez-Barrios P, et al.  Suicide gene therapy for treatment of retinoblastoma in a murine model. Hum Gene Ther. 1999;10:441–448
  98. Hurwitz RL, Chevez-Barrios P, Chintagumpala M, et al: Gene therapy for retinoblastoma. The Fourth Great Basin Visual Science Symposium, August 18, 2000. (Available at http://insight.med.utah.edu/gbs/gbs4/pdf/hurwitz_ paper.pdf)
  99. Ikuno Y, Leong FL, Kazlauskas A. Attenuation of experimental proliferative vitreoretinopathy by inhibiting the platelet-derived growth factor receptor. Invest Ophthalmol Vis Sci. 2000;41:3107–3116
  100. Isenmann S, Engel S, Kugler S, et al.  Intravitreal adenoviral gene transfer evokes an immune response in the retina that is directed against the heterologous lacZ transgene product but does not limit transgene expression. Brain Res. 2001;892:229–240
  101. Jomary C, Grist J, Milbrandt J, et al.  Epitope-tagged recombinant AAV vectors for expressing neurturin and its receptor in retinal cells. Mol Vis. 2001;7:36–41 Available at http://www.molvis.org/molvis/v7/a6/
  102. Jomary C, Piper TA, Dickson G, et al.  Adenovirus-mediated gene transfer to murine retinal cells in vitro and in vivo. FEBS Lett. 1994;347:117–122
  103. Jomary C, Vincent KA, Grist J, et al.  Rescue of photoreceptor function by AAV-mediated gene transfer in a mouse model of inherited retinal degeneration. Gene Ther. 1997;4:683–690
  104. Joseph RM, Li T. Overexpression of Bcl-2 or Bcl-XL transgenes and photoreceptor degeneration. Invest Ophthalmol Vis Sci. 1996;37:2434–2446
  105. Kaelin WG. Functions of the retinoblastoma protein. Bioessays. 1999;21:950–958
  106. Kaelin WG. Recent insights into the functions of the retinoblastoma susceptibility gene product. Cancer Invest. 1997;15:243–254
  107. Kampmeier J, Behrens A, Wang Y, et al.  Inhibition of rabbit keratocyte and human fetal lens epithelial cell proliferation by retrovirus-mediated transfer of antisense cyclin G1 and antisense MAT1 constructs. Hum Gene Ther. 2000;11:1–8
  108. Kaufman PL, Jia WW, Tan J, et al.  A perspective of gene therapy in the glaucomas. Surv Ophthalmol. 1999;43(Suppl 1):S91–S97
  109. Kedzierski W, Bok D, Travis GH. Non-cell-autonomous photoreceptor degeneration in rds mutant mice mosaic for expression of a rescue transgene. J Neurosci. 1998;18:4076–4082
  110. Kido M, Rich KA, Yang G, et al.  Use of a retroviral vector with an internal opsin promoter to direct gene expression to retinal photoreceptor cells. Curr Eye Res. 1996;15:833–844
  111. Kimura H, Sakamoto T, Cardillo JA, et al.  Retrovirus-mediated suicide gene transduction in the vitreous cavity of the eye (feasibility in prevention of proliferative vitreoretinopathy). Hum Gene Ther. 1996;7:799–808
  112. Knudson AG. Mutation and cancer (statistical study of retinoblastoma). Proc Natl Acad Sci USA. 1971;68:820–823
  113. Kogishi J, Miyatake S, Hangai M, et al.  Mutant herpes simplex virus-mediated suppression of retinoblastoma. Curr Eye Res. 1999;18:321–326
  114. Kukowska-Latallo JF, Bielinska AU, Johnson J, et al.  Efficient transfer of genetic material into mammalian cells using Starburst polyamidoamine dendrimers. Proc Natl Acad Sci USA. 1996;93:4897–4902
  115. Kumar-Singh R, Farber DB. Encapsidated adenovirus mini-chromosome-mediated delivery of genes to the retina (application to the rescue of photoreceptor degeneration). Hum Mol Genet. 1998;7:1893–1900
  116. Lacorazza HD, Jendoubi M. Correction of ornithine-delta-aminotransferase deficiency in a Chinese hamster ovary cell line mediated by retrovirus gene transfer. Gene Ther. 1995;2:22–28
  117. Lai CC, Gouras P, Doi K, et al.  Tracking RPE transplants labeled by retroviral gene transfer with green fluorescent protein. Invest Ophthalmol Vis Sci. 1999;40:2141–2146
  118. Lai CC, Wu WC, Chen SL, et al.  Suppression of choroidal neovascularization by adeno-associated virus vector expressing angiostatin. Invest Ophthalmol Vis Sci. 2001;42:2401–2407
  119. Lai CM, Shen WY, Constable I, Rakoczy PE. The use of adenovirus-mediated gene transfer to develop a rat model for photoreceptor degeneration. Invest Ophthalmol Vis Sci. 2000;41:580–584
  120. Lai CM, Shen WY, Constable IJ, Rakoczy PE. Preferential adenovirus-mediated transduction of cells at the sites of laser photocoagulation in the rat eye. Curr Eye Res. 1999;19:411–417
  121. Lai YKY, Rakoczy P, Constable I. Adeno-associated virus-mediated gene transfer into human retinal pigment epithelium cells. Aust NZ J Ophthalmol. 1998;26:S77–S79
  122. Larkin DF, Oral HB, Ring CJ, et al.  Adenovirus-mediated gene delivery to the corneal endothelium. Transplantation. 1996;61:363–370
  123. Lau D, McGee LH, Zhou S, et al.  Retinal degeneration is slowed in transgenic rats by AAV-mediated delivery of FGF-2. Invest Ophthalmol Vis Sci. 2000;41:3622–3633
  124. LaVail MM. Analysis of neurological mutants with inherited retinal degeneration. Friedenwald lecture. Invest Ophthalmol Vis Sci. 1981;21:638–657
  125. LaVail MM, Steinberg RH, Matthes MT. Protection from constant light damage by NT-3 overexpressed by the lens in transgenic mice. Invest Ophthalmol Vis Sci. 1997;38:S479; [abstract]
  126. LaVail MM, Unoki K, Yasumura D, et al.  Multiple growth factors, cytokines, and neurotrophins rescue photoreceptors from the damaging effects of constant light. Proc Natl Acad Sci USA. 1992;89:11249–11253
  127. LaVail MM, Yasumura D, Matthes MT, et al.  Ribozyme rescue of photoreceptor cells in P23H transgenic rats (long-term survival and late-stage therapy). Proc Natl Acad Sci USA. 2000;97:11488–11493
  128. Lem J, Flannery JG, Li T, et al.  Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP phosphodiesterase beta subunit. Proc Natl Acad Sci USA. 1992;89:4422–4426
  129. Leon A, Curtis R. Autosomal dominant rod-cone dysplasia in the Rdy cat. 1. Light and electron microscopic findings. Exp Eye Res. 1990;51:361–381
  130. Levin LA. Direct and indirect approaches to neuroprotective therapy of glaucomatous optic neuropathy. Surv Ophthalmol. 1999;43(Suppl 1):S98–101
  131. Lewin AS, Drenser KA, Hauswirth WW, et al.  Ribozyme rescue of photoreceptor cells in a transgenic rat model of autosomal dominant retinitis pigmentosa. Nat Med. 1998;4:967–971
  132. Lewis GP, Linberg KA, Geller SF, et al.  Effects of the neurotrophin brain-derived neurotrophic factor in an experimental model of retinal detachment. Invest Ophthalmol Vis Sci. 1999;40:1530–1544
  133. Li T, Adamian M, Roof DJ, et al.  In vivo transfer of a reporter gene to the retina mediated by an adenoviral vector. Invest Ophthalmol Vis Sci. 1994;35:2543–2549
  134. Li T, Davidson BL. Phenotype correction in retinal pigment epithelium in murine mucopolysaccharidosis VII by adenovirus-mediated gene transfer. Proc Natl Acad Sci USA. 1995;92:7700–7704
  135. Li ZY, Wong F, Chang JH, et al.  Rhodopsin transgenic pigs as a model for human retinitis pigmentosa. Invest Ophthalmol Vis Sci. 1998;39:808–819
  136. Liang FQ, Dejneka NS, Cohen DR, et al.  AAV-mediated delivery of ciliary neurotrophic factor prolongs photoreceptor survival in the rhodopsin knockout mouse. Mol Ther. 2001;3:241–248
  137. Liu C, Li Y, Peng M, et al.  Activation of caspase-3 in the retina of transgenic rats with the rhodopsin mutation s334ter during photoreceptor degeneration. J Neurosci. 1999;19:4778–4785
  138. Liu X, Brandt CR, Gabelt BT, et al.  Herpes simplex virus mediated gene transfer to primate ocular tissues. Exp Eye Res. 1999;69:385–395
  139. Lolley RN, Farber DB, Rayborn ME, Hollyfield JG. Cyclic GMP accumulation causes degeneration of photoreceptor cells (simulation of an inherited disease). Science. 1977;196:664–666
  140. Lolley RN, Rong H, Craft CM. Linkage of photoreceptor degeneration by apoptosis with inherited defect in phototransduction. Invest Ophthalmol Vis Sci. 1994;35:358–362
  141. Madreperla SA, Whittum-Hudson JA, Prendergast RA, et al.  Intraocular tumor suppression of retinoblastoma gene-reconstituted retinoblastoma cells. Cancer Res. 1991;51:6381–6384
  142. Mah SP, Zhong LT, Liu Y, et al.  The protooncogene bcl-2 inhibits apoptosis in PC12 cells. J Neurochem. 1993;60:1183–1186
  143. Malecaze F, Couderc B, de Neuville S, et al.  Adenovirus-mediated suicide gene transduction (feasibility in lens epithelium and in prevention of posterior capsule opacification in rabbits). Hum Gene Ther. 1999;10:2365–2372
  144. Marlhens F, Bareil C, Griffoin JM, et al.  Mutations in RPE65 cause Lebers congenital amaurosis. Nat Genet. 1997;17:139–141
  145. Mashhour B, Couton D, Perricaudet M, Briand P. In vivo adenovirus-mediated gene transfer into ocular tissues. Gene Ther. 1994;1:122–126
  146. Masuda I, Matsuo T, Yasuda T, Matsuo N. Gene transfer with liposomes to the intraocular tissues by different routes of administration. Invest Ophthalmol Vis Sci. 1996;37:1914–1920
  147. Matthes M, Yasumura D, Yancopoulos G. Activation of CNTF and BDNF receptors in the retina (role in photoreceptor rescue). Invest Ophthalmol Vis Sci. 1995;36:S252; [abstract]
  148. McGee Sanftner LH, Rendahl KG, Quiroz D, et al.  Recombinant AAV-mediated delivery of a tet-inducible reporter gene to the rat retina. Mol Ther. 2001;3:688–696
  149. McLaren MJ, Inana G. Inherited retinal degeneration (basic FGF induces phagocytic competence in cultured RPE cells from RCS rats). FEBS Lett. 1997;412:21–29
  150. McLaughlin ME, Sandberg MA, Berson EL, Dryja TP. Recessive mutations in the gene encoding the beta-subunit of rod phosphodiesterase in patients with retinitis pigmentosa. Nat Genet. 1993;4:130–134
  151. McNally N, Kenna P, Humphries MM, et al.  Structural and functional rescue of murine rod photoreceptors by human rhodopsin transgene. Hum Mol Genet. 1999;8:1309–1312
  152. Milam AH. Strategies for rescue of retinal photoreceptor cells. Curr Opin Neurobiol. 1993;3:797–804
  153. Miyoshi H, Takahashi M, Gage FH, Verma IM. Stable and efficient gene transfer into the retina using an HIV-based lentiviral vector. Proc Natl Acad Sci USA. 1997;94:10319–10323
  154. Mori K, Duh E, Gehlbach P, et al.  Pigment epithelium-derived factor inhibits retinal and choroidal neovascularization. J Cell Physiol. 2001;188:253–263
  155. Muncaster MM, Cohen BL, Phillips RA, Gallie BL. Failure of RB1 to reverse the malignant phenotype of human tumor cell lines. Cancer Res. 1992;52:654–661
  156. Murata T, Cui J, Taba KE, et al.  The possibility of gene therapy for the treatment of choroidal neovascularization. Ophthalmology. 2000;107:1364–1373
  157. Murata T, Hangai M, Ishibashi T, et al.  Retrovirus-mediated gene transfer to photocoagulation-induced choroidal neovascular membranes. Invest Ophthalmol Vis Sci. 1998;39:2474–2478
  158. Murata T, Hoffmann S, Ishibashi T, et al.  Retrovirus-mediated gene transfer targeted to retinal photocoagulation sites. Diabetologia. 1998;41:500–506
  159. Nabel GJ, Nabel EG, Yang ZY, et al.  Direct gene transfer with DNA-liposome complexes in melanoma (expression, biologic activity, and lack of toxicity in humans). Proc Natl Acad Sci USA. 1993;90:11307–11311
  160. Naldini L, Blomer U, Gage FH, et al.  Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc Natl Acad Sci USA. 1996;93:11382–11388
  161. Naldini L, Blomer U, Gallay P, et al.  In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science. 1996;272:263–267
  162. Nir I, Kedzierski W, Chen J, Travis GH. Expression of Bcl-2 protects against photoreceptor degeneration in retinal degeneration slow (rds) mice. J Neurosci. 2000;20:2150–2154
  163. O'Neill B, Millington-Ward S, O'Reilly M, et al.  Ribozyme-based therapeutic approaches for autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2000;41:2863–2869
  164. Ogata N, Otsuji T, Matsushima M, et al.  Phosphorothioate oligonucleotides induction into experimental choroidal neovascularization by HVJ-liposome system. Curr Eye Res. 1999;18:261–269
  165. Oral HB, Larkin DF, Fehervari Z, et al.  Ex vivo adenovirus-mediated gene transfer and immunomodulatory protein production in human cornea. Gene Ther. 1997;4:639–647
  166. Oshima Y, Sakamoto T, Yamanaka I, et al.  Targeted gene transfer to corneal endothelium in vivo by electric pulse. Gene Ther. 1998;5:1347–1354
  167. Osusky R, Jiang M, Buchi ER, et al.  beta-Galactosidase transgene expression in transplanted rabbit retinal pigment epithelial cells in vivo. Graefes Arch Clin Exp Ophthalmol. 1995;233:220–225
  168. Otsuji T, Ogata N, Takahashi K, et al.  In vivo gene transfer into choroidal neovascularization by the HVJ liposome method. Graefes Arch Clin Exp Ophthalmol. 2000;238:191–199
  169. Pagon RA. Retinitis pigmentosa. Surv Ophthalmol. 1988;33:137–177
  170. Perry J, Du J, Kjeldbye H, Gouras P. The effects of bFGF on RCS rat eyes. Curr Eye Res. 1995;14:585–592
  171. Phelan JK, Bok D. A brief review of retinitis pigmentosa and the identified retinitis pigmentosa genes. Mol Vis. 2000;6:116–124 Available at http://www.molvis.org/molvis/v6/a16
  172. Rakoczy PE, Lai MC, Baines MG, et al.  Expression of cathepsin S antisense transcripts by adenovirus in retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 1998;39:2095–2104
  173. Rasmussen H, Chu KW, Campochiaro P, et al.  Clinical protocol. An open-label, phase I, single administration, dose- escalation study of ADGVPEDF.11D (ADPEDF) in neovascular age-related macular degeneration (AMD). Hum Gene Ther. 2001;12:2029–2032
  174. Reichel MB, Ali RR, Thrasher AJ, et al.  Immune responses limit adenovirally mediated gene expression in the adult mouse eye. Gene Ther. 1998;5:1038–1046
  175. Reichel MB, Bainbridge J, Baker D, et al.  An immune response after intraocular administration of an adenoviral vector containing a beta galactosidase reporter gene slows retinal degeneration in the rd mouse. Br J Ophthalmol. 2001;85:341–344
  176. Ritter T, Vogt K, Rieck P, et al.  Adenovirus-mediated gene transfer of interleukin-4 to corneal endothelial cells and organ cultured corneas leads to high IL-4 expression. Exp Eye Res. 1999;69:563–568
  177. Rivero JL, Lacorazza HD, Kozhich A, et al.  Retrovirus-mediated gene transfer and expression of human ornithine delta-aminotransferase into embryonic fibroblasts. Hum Gene Ther. 1994;5:701–707
  178. Robbins SG, Mixon RN, Wilson DJ, et al.  Platelet-derived growth factor ligands and receptors immunolocalized in proliferative retinal diseases. Invest Ophthalmol Vis Sci. 1994;35:3649–3663
  179. Roy S, Zhang K, Roth T, et al.  Reduction of fibronectin expression by intravitreal administration of antisense oligonucleotides. Nat Biotechnol. 1999;17:476–479
  180. Ruiz A, Brett P, Bok D. TIMP-3 is expressed in the human retinal pigment epithelium. Biochem Biophys Res Commun. 1996;226:467–474
  181. Sakamoto T, Kimura H, Scuric Z, et al.  Inhibition of experimental proliferative vitreoretinopathy by retroviral vector-mediated transfer of suicide gene. Can proliferative vitreoretinopathy be a target of gene therapy?. Ophthalmology. 1995;102:1417–1424
  182. Sakamoto T, Oshima Y, Nakagawa K, et al.  Target gene transfer of tissue plasminogen activator to cornea by electric pulse inhibits intracameral fibrin formation and corneal cloudiness. Hum Gene Ther. 1999;10:2551–2557
  183. Sakamoto T, Ueno H, Goto Y, et al.  Retinal functional change caused by adenoviral vector-mediated transfection of LacZ gene. Hum Gene Ther. 1998;9:789–799
  184. Samulski RJ, Zhu X, Xiao X, et al.  Targeted integration of adeno-associated virus (AAV) into human chromosome 19. EMBO J. 1991;10:3941–3950
  185. Sands MS, Wolfe JH, Birkenmeier EH, et al.  Gene therapy for murine mucopolysaccharidosis type VII. Neuromuscul Disord. 1997;7:352–360
  186. Sanyal S, Chader G, Aguirre G: Expression of retinal degeneration slow (rds) gene in the retina of the mouse, in Lavail MM, Hollyfield JG, Anderson RE (eds): Retinal Degeneration: Experimental and Clinical Studies. New York, Alan R. Liss, pp 239–56, 1985
  187. Sarra GM, Stephens C, de Alwis M, et al.  Gene replacement therapy in the retinal degeneration slow (rds) mouse (the effect on retinal degeneration following partial transduction of the retina). Hum Mol Genet. 2001;10:2353–2361
  188. Schubert CA, Kimura H, Spee C, et al.  Retrovirus-mediated transfer of the suicide gene into retinal pigment epithelial cells in vitro. Curr Eye Res. 1997;16:656–662
  189. Schweigerer L, Malerstein B, Neufeld G, Gospodarowicz D. Basic fibroblast growth factor is synthesized in cultured retinal pigment epithelial cells. Biochem Biophys Res Commun. 1987;143:934–940
  190. Seigel GM, Chiu L, Paxhia A. Inhibition of neuroretinal cell death by insulin-like growth factor-1 and its analogs. Mol Vis. 2000;6:157–163 org/molvis/v6/a21) Available at http://www.molvis
  191. Shaw LC, Skold A, Wong F, et al.  An allele-specific hammerhead ribozyme gene therapy for a porcine model of autosomal dominant retinitis pigmentosa. Mol Vis. 2001;7:6–13
  192. Shaw LC, Skold A, Wong F. An allele-specific hammerhead ribozyme gene therapy for a porcine model of autosomal dominant retinitis pigmentosa. Mol Vis. 2000;7:6–13
  193. Shen WY, Lai MC, Beilby J, et al.  Combined effect of cyclosporine and sirolimus on improving the longevity of recombinant adenovirus-mediated transgene expression in the retina. Arch Ophthalmol. 2001;119:1033–1043
  194. Simell O, Takki K. Raised plasma-ornithine and gyrate atrophy of the choroid and retina. Lancet. 1973;1:1031–1033
  195. Simon PD, Vorwerk CK, Mansukani SS, et al.  bcl-2 gene therapy exacerbates excitotoxicity. Hum Gene Ther. 1999;10:1715–1720
  196. Spencer B, Agarwala S, Gentry L, Brandt CR. HSV-1 vector-delivered FGF2 to the retina is neuroprotective but does not preserve functional responses. Mol Ther. 2001;3:746–756
  197. Spencer B, Agarwala S, Miskulin M, et al.  Herpes simplex virus-mediated gene delivery to the rodent visual system. Invest Ophthalmol Vis Sci. 2000;41:1392–1401
  198. Stewart MJ, Plautz GE, Del Buono L, et al.  Gene transfer in vivo with DNA-liposome complexes (safety and acute toxicity in mice). Hum Gene Ther. 1992;3:267–275
  199. Stramm LE, Wolfe JH, Schuchman EH, et al.  Beta-glucuronidase mediated pathway essential for retinal pigment epithelial degradation of glycosaminoglycans. Disease expression and in vitro disease correction using retroviral mediated cDNA transfer. Exp Eye Res. 1990;50:521–532
  200. Streilein JW. Ocular immune privilege and the Faustian dilemma. The Proctor lecture. Invest Ophthalmol Vis Sci. 1996;37:1940–1950
  201. Sullenger BA, Cech TR. Ribozyme-mediated repair of defective mRNA by targeted, trans-splicing. Nature. 1994;371:619–622
  202. Sullivan DM, Chung DC, Anglade E, et al.  Adenovirus-mediated gene transfer of ornithine aminotransferase in cultured human retinal pigment epithelium. Invest Ophthalmol Vis Sci. 1996;37:766–774
  203. Sullivan DM, Jensen TG, Taichman LB, Csaky KG. Ornithine-delta-aminotransferase expression and ornithine metabolism in cultured epidermal keratinocytes (toward metabolic sink therapy for gyrate atrophy). Gene Ther. 1997;4:1036–1044
  204. Szekely L, Wang Y, Klein G, Wiman KG. RB-reconstituted human retinoblastoma cells form RB-positive intraocular and intracerebral but not subcutaneous tumors in SCID mice. Int J Cancer. 1995;61:683–691
  205. Takagi H, Yoshimura N, Tanihara H, Honda Y. Insulin-like growth factor-related genes, receptors, and binding proteins in cultured human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 1994;35:916–923
  206. Takahashi M, Miyoshi H, Verma IM, Gage FH. Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer. J Virol. 1999;73:7812–7816
  207. Tanelian DL, Barry MA, Johnston SA, et al.  Controlled gene gun delivery and expression of DNA within the cornea. Biotechniques. 1997;23:484–488
  208. Tao W, Sherman S, O'Rourke P. Encapsulated cell based intraocular delivery of CNTF reduces inherited retinal degeneration in an rcd 1 dog model. Invest Ophthalmol Vis Sci. 2001;42:S173; [abstract]
  209. Travis GH, Groshan KR, Lloyd M, Bok D. Complete rescue of photoreceptor dysplasia and degeneration in transgenic retinal degeneration slow (rds) mice. Neuron. 1992;9:113–119
  210. Tripathy SK, Black HB, Goldwasser E, Leiden JM. Immune responses to transgene-encoded proteins limit the stability of gene expression after injection of replication-defective adenovirus vectors. Nat Med. 1996;2:545–550
  211. Tsang SH, Chen J, Kjeldbye H, et al.  Retarding photoreceptor degeneration in Pdegtm1/Pdegtml mice by an apoptosis suppressor gene. Invest Ophthalmol Vis Sci. 1997;38:943–950
  212. Tso MO, Zhang C, Abler AS, et al.  Apoptosis leads to photoreceptor degeneration in inherited retinal dystrophy of RCS rats. Invest Ophthalmol Vis Sci. 1994;35:2693–2699
  213. Unoki K, LaVail MM. Protection of the rat retina from ischemic injury by brain-derived neurotrophic factor, ciliary neurotrophic factor, and basic fibroblast growth factor. Invest Ophthalmol Vis Sci. 1994;35:907–915
  214. Uteza Y, Rouillot JS, Kobetz A, et al.  Intravitreous transplantation of encapsulated fibroblasts secreting the human fibroblast growth factor 2 delays photoreceptor cell degeneration in Royal College of Surgeons rats. Proc Natl Acad Sci USA. 1999;96:3126–3131
  215. Vollrath D, Feng W, Duncan JL, et al.  Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk. Proc Natl Acad Sci USA. 2001;98:12584–12589
  216. Waldbillig RJ, Pfeffer BA, Schoen TJ, et al.  Evidence for an insulin-like growth factor autocrine-paracrine system in the retinal photoreceptor-pigment epithelial cell complex. J Neurochem. 1991;57:1522–1533
  217. Weintraub SJ, Prater CA, Dean DC. Retinoblastoma protein switches the E2F site from positive to negative element. Nature. 1992;358:259–261
  218. White JB, Taylor RE, Pittler SJ. Reproducible high efficiency gene transfer into Y79 retinoblastoma cells using adenofection. J Neurosci Methods. 2001;106:1–7
  219. White K, Tahaoglu E, Steller H. Cell killing by the Drosophila gene reaper. Science. 1996;271:805–807
  220. Wolfe JH, Sands MS, Barker JE, et al.  Reversal of pathology in murine mucopolysaccharidosis type VII by somatic cell gene transfer. Nature. 1992;360:749–753
  221. Wong CA, Jia W, Matsubara JA. Experimental gene therapy for an in vitro model of proliferative vitreoretinopathy. Can J Ophthalmol. 1999;34:379–384
  222. Wrobel I, Collins D. Fusion of cationic liposomes with mammalian cells occurs after endocytosis. Biochim Biophys Acta. 1995;1235:296–304
  223. Xiao M, Sastry SM, Li ZY, et al.  Effects of retinal laser photocoagulation on photoreceptor basic fibroblast growth factor and survival. Invest Ophthalmol Vis Sci. 1998;39:618–630
  224. Xu D, Bureau Y, McIntyre DC, et al.  Attenuation of ischemia-induced cellular and behavioral deficits by X chromosome-linked inhibitor of apoptosis protein overexpression in the rat hippocampus. J Neurosci. 1999;19:5026–5033
  225. Xu HJ, Sumegi J, Hu SX, et al.  Intraocular tumor formation of RB reconstituted retinoblastoma cells. Cancer Res. 1991;51:4481–4485
  226. Xu HJ, Zhou Y, Ji W, et al.  Reexpression of the retinoblastoma protein in tumor cells induces senescence and telomerase inhibition. Oncogene. 1997;15:2589–2596
  227. Xu Y, Szoka FC. Mechanism of DNA release from cationic liposome/DNA complexes used in cell transfection. Biochemistry. 1996;35:5616–5623
  228. Young RW. Pathophysiology of age-related macular degeneration. Surv Ophthalmol. 1987;31:291–306
  229. Zack DJ, Dean M, Molday RS, et al.  What can we learn about age-related macular degeneration from other retinal diseases?. Mol Vis. 1999;5:30; molvis.org/molvis/v5/a30) Available at http://www
  230. Zhang X, Bok D. Transplantation of retinal pigment epithelial cells and immune response in the subretinal space. Invest Ophthalmol Vis Sci. 1998;39:1021–1027
  231. Zufferey R, Dull T, Mandel RJ, et al.  Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J Virol. 1998;72:9873–9880

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Survey of Ophthalmology
Volume 47, Issue 5 , Pages 449-469 , September 2002

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