Skip to main content

Inherited Retinal Diseases

  • Chapter
  • First Online:
Vitreoretinal Disorders

Abstract

The successful sequencing of the human genome and invention of new molecular tools such as gene modification technologies and virus-mediated gene delivery systems have changed our understanding and treatment approaches toward inherited retinal disorders. This chapter includes the most recent advances that showed potential benefits in clinical trials and brought hope for patients with visually debilitating inherited diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Sohocki MM, Daiger SP, Bowne SJ, Rodriquez JA, Northrup H, Heckenlively JR, Birch DG, Mintz-Hittner H, Ruiz RS, Lewis RA, Saperstein DA, Sullivan LS. Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies. Hum Mutat. 2001;17(1):42–51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Berger W, Kloeckener-Gruissem B, Neidhardt J. The molecular basis of human retinal and vitreoretinal diseases. Prog Retin Eye Res. 2010;29(5):335–75.

    Article  PubMed  CAS  Google Scholar 

  3. den Hollander AI, Roepman R, Koenekoop RK, Cremers FPM. Leber congenital amaurosis: Genes, proteins and disease mechanisms. Prog Retin Eye Res. 2008;27(4):391–419.

    Article  CAS  Google Scholar 

  4. Cremers FPM, van den Hurk JAJM, den Hollander AI. Molecular genetics of Leber congenital amaurosis. Hum Mol Genet. 2002;11(10):1169–76.

    Article  PubMed  CAS  Google Scholar 

  5. Perrault I, Rozet J-M, Gerber S, Ghazi I, Leowski C, Ducroq D, Souied E, Dufier J-L, Munnich A, Kaplan J. Leber congenital amaurosis. Mol Genet Metab. 1999;68(2):200–8.

    Article  PubMed  CAS  Google Scholar 

  6. Dharmaraj SR, Silva ER, Pina AL, Li YY, Yang JM, Carter CR, Loyer MK, El-Hilali HK, Traboulsi EK, Sundin OK, Zhu DK, Koenekoop RK, Maumenee IH. Mutational analysis and clinical correlation in Leber congenital amaurosis. Ophthalmic Genet. 2000;21(3):135–50.

    Article  PubMed  CAS  Google Scholar 

  7. Jin M, Li S, Moghrabi WN, Sun H, Travis GH. Rpe65 Is the Retinoid Isomerase in Bovine Retinal Pigment Epithelium. Cell. 2005;122(3):449–59.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Mussolino C, della Corte M, Rossi S, Viola F, Di Vicino U, Marrocco E, Neglia S, Doria M, Testa F, Giovannoni R, Crasta M, Giunti M, Villani E, Lavitrano M, Bacci ML, Ratiglia R, Simonelli F, Auricchio A, Surace EM. AAV-mediated photoreceptor transduction of the pig cone-enriched retina. Gene Ther. 2011;18(7):637–45.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Cideciyan AV. Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy. Prog Retin Eye Res. 2010;29(5):398–427.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Bainbridge JWB, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, Viswanathan A, Holder GE, Stockman A, Tyler N, Petersen-Jones S, Bhattacharya SS, Thrasher AJ, Fitzke FW, Carter BJ, Rubin GS, Moore AT, Ali RR. Effect of gene therapy on visual function in Leber’s congenital amaurosis. N Engl J Med. 2008;358(21):2231–9.

    Article  PubMed  CAS  Google Scholar 

  11. Maguire AM, Simonelli F, Pierce EA, Pugh EN, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell’Osso L, Hertle R, Ma J, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med. 2008;358(21):2240–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Hauswirth WW, Aleman TS, Kaushal S, Cideciyan AV, Schwartz SB, Wang L, Conlon TJ, Boye SL, Flotte TR, Byrne BJ, Jacobson SG. Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum Gene Ther. 2008;19(10):979–90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Cideciyan AV, Aleman TS, Boye SL, Schwartz SB, Kaushal S, Roman AJ, Pang J-J, Sumaroka A, Windsor EAM, Wilson JM, Flotte TR, Fishman GA, Heon E, Stone EM, Byrne BJ, Jacobson SG, Hauswirth WW. Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proc Natl Acad Sci. 2008;105(39):15112–7.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Russell S, Bennett J, Wellman JA, Chung DC, Yu Z-F, Tillman A, Wittes J, Pappas J, Elci O, McCague S, Cross D, Marshall KA, Walshire J, Kehoe TL, Reichert H, Davis M, Raffini L, George LA, Hudson FP, Dingfield L, Zhu X, Haller JA, Sohn EH, Mahajan VB, Pfeifer W, Weckmann M, Johnson C, Gewaily D, Drack A, Stone E, Wachtel K, Simonelli F, Leroy BP, Wright JF, High KA, Maguire AM. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65 -mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017;390(10097):849860.

    Article  Google Scholar 

  15. Sankila E-M, Tolvanen R, van den Hurk JAJM, Cremers FPM, de la Chapelle A. Aberrant splicing of the CHM gene is a significant cause of choroideremia. Nat Genet. 1992;1(2):109–13.

    Article  PubMed  CAS  Google Scholar 

  16. Seabra MC, Brown MS, Goldstein JL. Retinal degeneration in choroideremia: deficiency of rab geranylgeranyl transferase. Science. 1993;259(5093):377–81.

    Article  PubMed  CAS  Google Scholar 

  17. Jacobson SG, Cideciyan AV, Sumaroka A, Aleman TS, Schwartz SB, Windsor EAM, Roman AJ, Stone EM, MacDonald IM. Remodeling of the human retina in choroideremia: rab escort protein 1 ( REP-1 ) mutations. Investig Opthalmology Vis Sci. 2006;47(9):4113.

    Article  Google Scholar 

  18. MacLaren RE, Groppe M, Barnard AR, Cottriall CL, Tolmachova T, Seymour L, Clark KR, During MJ, Cremers FPM, Black GCM, Lotery AJ, Downes SM, Webster AR, Seabra MC. Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. Lancet. 2014;383(9923):1129–37.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Stargardt KB. Über familiäre, progressive Degeneration in der Makulagegend des Auges (in German). Albrecht von Graefes Archiv für Ophthalmologie. 1909;71:534–50.

    Article  Google Scholar 

  20. Quazi F, Lenevich S, Molday RS. ABCA4 is an Nretinylidene-phosphatidylethanolamine and phosphatidylethanolamine importer. Nat Commun. 2012;3:925.

    Article  PubMed  CAS  Google Scholar 

  21. Tsybovsky Y, Molday RS, Palczewski K. The ATP-binding cassette transporter ABCA4: structural and functional properties and role in retinal disease. Adv Exp Med Biol. 2010;703:105–25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Fujinami K, et al. Clinical and molecular characteristics of childhood-onset Stargardt disease. Ophthalmology. 2015;122:326–34.

    Article  PubMed  Google Scholar 

  23. Stone EM, Andorf JL, Whitmore SS, DeLuca AP, Giacalone JC, Streb LM, Braun TA, Mullins RF, Scheetz TE, Sheffield VC, Tucker BA. Clinically focused molecular investigation of 1000 consecutive families with inherited retinal disease. Ophthalmology. 2017;124(9):1314–31.

    Article  PubMed  Google Scholar 

  24. Martínez-Mir A, Paloma E, Allikmets R, Ayuso C, del Rio T, Dean M, Vilageliu L, Gonzàlez-Duarte R, Balcells S. Retinitis pigmentosa caused by a homozygous mutation in the Stargardt disease gene ABCR. Nat Genet. 1998;18(1):11–2.

    Article  PubMed  Google Scholar 

  25. Cremers FP, van de Pol DJ, van Driel M, den Hollander AI, van Haren FJ, Knoers NV, Tijmes N, Bergen AA, Rohrschneider K, Blankenagel A, Pinckers AJ, Deutman AF, Hoyng CB. Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt’s disease gene ABCR. Hum Mol Genet. 1998;7(3):355–62.

    Article  PubMed  CAS  Google Scholar 

  26. Zhang K, Kniazeva M, Han M, Li W, Yu Z, Yang Z, Li Y, Metzker ML, Allikmets R, Zack DJ, Kakuk LE, Lagali PS, Wong PW, MacDonald IM, Sieving PA, Figueroa DJ, Austin CP, Gould RJ, Ayyagari R, Petrukhin K. A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy. Nat Genet. 2001;27(1):89–93.

    Article  PubMed  CAS  Google Scholar 

  27. Palejwala NV, Gale MJ, Clark RF, Schlechter C, Weleber RG, Pennesi ME. Insights into autosomal dominant stargardt-like macular dystrophy through multimodality diagnostic imaging. Retina. 2016;36(1):119–30.

    Article  PubMed  Google Scholar 

  28. Lu LJ, Liu J, Adelman RA. Novel therapeutics for Stargardt disease. Graefes Arch Clin Exp Ophthalmol. 2017;255(6):1057–62.

    Article  PubMed  CAS  Google Scholar 

  29. Yanoff M, Duker JS. Ophthalmology. 3rd ed. Edinburgh: Mosby; 2008. p. 560–2.

    Google Scholar 

  30. Deutman A, Hoyng C, van Lith-Verhoeven J. Macular dystrophies, Retina. 4th ed. Mosby: Elsevier; 2006. p. 1171–4.

    Google Scholar 

  31. Sparrow JR, Boulton M. RPE lipofuscin and its role in retinal pathobiology. Exp Eye Res. 2005;80:595–606.

    Article  PubMed  CAS  Google Scholar 

  32. Chen Y, Roorda A, Duncan JL. Advances in imaging of Stargardt disease. Adv Exp Med Biol. 2010;664:333–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. “WORLD FIRST FOR STARGARDT’S DISEASE”. Optometry Today. 6 July 2016.

  34. Alkeus Pharmaceuticals. “Alkeus Pharmaceuticals: Developing Treatments for Dry-AMD & Stargardt disease”. www.alkeuspharma.com.

  35. “Phase 2 Tolerability and Effects of ALK-001 on Stargardt Disease - Full Text View - ClinicalTrials.gov”. clinicaltrials.gov

  36. Decensi A, et al. Fenretinide and risk reduction of second breast cancer. Nat Clin Pract Oncol. 2007;4:64–5.

    Article  PubMed  Google Scholar 

  37. Mata NL, Lichter JB, Vogel R, et al. Investigation of oral fenretinide for treatment of geographic atrophy in age-related macular degeneration. Retina. 2013;33:498–507.

    Article  PubMed  CAS  Google Scholar 

  38. Dobri N, et al. A1120, a nonretinoid RBP4 antagonist, inhibits formation of cytotoxic bisretinoids in the animal model of enhanced retinal lipofuscinogenesis. Invest Ophthalmol Vis Sci. 2013;54:85–95.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Schwartz SD, Regillo CD, Lam BL, Eliott D, Rosenfeld PJ, Gregori NZ, Hubschman JP, Davis JL, Heilwell G, Spirn M, Maguire J, Gay R, Bateman J, Ostrick RM, Morris D, Vincent M, Anglade E, Del Priore LV, Lanza R. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet (London, England). 2015;385(9967):509–16.

    Article  Google Scholar 

  40. Phase I/II a study of StarGen in patients with Stargardt macular degeneration. https://clinicaltrials.gov/ct2/show/NCT01367444?term=StarGen&rank=1.

  41. A study to determine the long-term safety, tolerability and biological activity of StarGen in patients with Stargardt’s macular degeneration. https://clinicaltrials.gov/ct2/show/NCT01736592?term=StarGen&rank=2.

  42. Binley K, Widdowson P, Loader J, Kelleher M, Iqball S, Ferrige G, de Belin J, Carlucci M, Angell-Manning D, Hurst F, Ellis S, Miskin J, Fernandes A, Wong P, Allikmets R, Bergstrom C, Aaberg T, Yan J, Kong J, Gouras P, Prefontaine A, Vezina M, Bussieres M, Naylor S, Mitrophanous KA. Transduction of photoreceptors with equine infectious anemia virus lentiviral vectors: safety and biodistribution of StarGen for Stargardt disease. Invest Ophthalmol Vis Sci. 2013;54(6):4061–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Lee K, Garg S. Navigating the current landscape of clinical genetic testing for inherited retinal dystrophies. Genet Med. 2015;17(4):245–52.

    Article  PubMed  CAS  Google Scholar 

  44. Mamanova L, Coffey AJ, Scott CE, et al. Target-enrichment strategies for next-generation sequencing. Nat Methods. 2010;7(2):111–8.

    Article  PubMed  CAS  Google Scholar 

  45. Audo I, Bujakowska KM, Leveillard T, et al. Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects Special Report Chiang, Lamey, McLaren, Thompson, Montgomery & De Roach 1274 Expert Rev. Mol. Diagn. 15(10), (2015) underlying retinal diseases. Orphanet J Rare Dis. 2012;7:8.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Majewski J, Schwartzentruber J, Lalonde E, et al. What can exome sequencing do for you? J Med Genet. 2011;48(9):580–9.

    Article  PubMed  CAS  Google Scholar 

  47. Rabbani B, Tekin M, Mahdieh N. The promise of whole-exome sequencing in medical genetics. J Hum Genet. 2014;59(1):5–15.

    Article  PubMed  CAS  Google Scholar 

  48. Singleton AB. Exome sequencing: a transformative technology. Lancet Neurol. 2011;10(10):942–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Consugar MB, Navarro-Gomez D, Place EM, et al. Panel-based genetic diagnostic testing for inherited eye diseases is highly accurate and reproducible, and more sensitive for variant detection, than exome sequencing. Genet Med. 2015;17(4):253–61.

    Article  PubMed  CAS  Google Scholar 

  50. Palazzo AF, Gregory TR. The case for junk DNA. PLoS Genet. 2014;10(5):e1004351.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. RetNet—Retinal information network. Laboratory for the molecular diagnosis of inherited eye diseases. Available from: https://sph.uth.edu/Retnet/.

  52. Strauss O. The retinal pigment epithelium in visual function. Physiol Rev. 2005;85(3):845–81.

    Article  PubMed  CAS  Google Scholar 

  53. Miller SS, Edelman JL. Active ion transport pathways in the bovine retinal pigment epithelium. J Physiol. 1990;424:283–300.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Ambati J, Ambati BK, Yoo SH, Ianchulev S, Adamis AP. Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies. Surv Ophthalmol. 2003;48(3):257–93.

    Article  PubMed  Google Scholar 

  55. Velez-Montoya R, Oliver SCN, Olson JL, Fine SL, Mandava N, Quiroz-Mercado H. Current knowledge and trends in age-related macular degeneration. Retina. 2013;33(8):1487–502.

    Article  PubMed  CAS  Google Scholar 

  56. Grunwald JE, Daniel E, Huang J, Ying G, Maguire MG, Toth CA, Jaffe GJ, Fine SL, Blodi B, Klein ML, Martin AA, Hagstrom SA, Martin DF, CATT Research Group. Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2014;121(1):150–61.

    Article  PubMed  Google Scholar 

  57. Zarbin MA, Casaroli-Marano RP, Rosenfeld PJ. Age-related macular degeneration: clinical findings, histopathology and imaging techniques. Dev Ophthalmol. 2014;53:1–32.

    Article  PubMed  Google Scholar 

  58. Li LX, Turner JE. Inherited retinal dystrophy in the RCS rat: prevention of photoreceptor degeneration by pigment epithelial cell transplantation. Exp Eye Res. 1988;47(6):911–7.

    Article  PubMed  CAS  Google Scholar 

  59. Gouras P, Kong J, Tsang SH. Retinal degeneration and RPE transplantation in Rpe65(−/−) mice. Invest Ophthalmol Vis Sci. 2002;43(10):3307–11.

    PubMed  Google Scholar 

  60. Boulton M, Marshall J, Mellerio J. Human retinal pigment epithelial cells in tissue culture: a means of studying inherited retinal diseases. Birth Defects Orig Artic Ser. 1982;18:101–18.

    PubMed  CAS  Google Scholar 

  61. Mason C, Dunnill P. Quantities of cells used for regenerative medicine and some implications for clinicians and bioprocessors. Regen Med. 2009;4(2):153–7.

    Article  PubMed  Google Scholar 

  62. Peyman GA, Blinder KJ, Paris CL, Alturki W, Nelson NC, Desai U. A technique for retinal pigment epithelium transplantation for age-related macular degeneration secondary to extensive subfoveal scarring. Ophthalmic Surg. 1991;22(2):102–8.

    PubMed  CAS  Google Scholar 

  63. Stanga PE, Kychenthal A, Fitzke FW, Halfyard AS, Chan R, Bird AC, Aylward GW. Retinal pigment epithelium translocation and central visual function in age related macular degeneration: preliminary results. Int Ophthalmol. 2001;23(4–6):297–307.

    Article  PubMed  CAS  Google Scholar 

  64. Hu DN, McCormick SA, Ritch R. Isolation and culture of iris pigment epithelium from iridectomy specimens of eyes with and without exfoliation syndrome. Arch Ophthalmol. 1997;115(1):89–94.

    Article  PubMed  CAS  Google Scholar 

  65. Crafoord S, Geng L, Seregard S, Algvere PV. Photoreceptor survival in transplantation of autologous iris pigment epithelial cells to the subretinal space. Acta Ophthalmol Scand. 2002;80(4):387–94.

    Article  PubMed  Google Scholar 

  66. Dintelmann TS, Heimann K, Kayatz P, Schraermeyer U. Comparative study of ROS degradation by IPE and RPE cells in vitro. Graefes Arch Clin Exp Ophthalmol. 1999;237(10):830–9.

    Article  PubMed  CAS  Google Scholar 

  67. Abe T, Yoshida M, Yoshioka Y, Wakusawa R, Tokitaishikawa Y, Seto H, Tamai M, Nishida K. Iris pigment epithelial cell transplantation for degenerative retinal diseases. Prog Retin Eye Res. 2007;26(3):302–21.

    Article  PubMed  CAS  Google Scholar 

  68. Schwartz SD, Hubschman J-P, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM, Mickunas E, Gay R, Klimanskaya I, Lanza R. Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet. 2012;379(9817):713–20.

    Article  PubMed  CAS  Google Scholar 

  69. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858):1917–20.

    Article  PubMed  CAS  Google Scholar 

  70. Ilic D, Devito L, Miere C, Codognotto S. Human embryonic and induced pluripotent stem cells in clinical trials: Table 1. Br Med Bull. 2015;36(1):ldv045.

    Article  Google Scholar 

  71. Barnea-Cramer AO, Wang W, Lu S-J, Singh MS, Luo C, Huo H, Mcclements ME, Barnard AR, Maclaren RE, Lanza R. Function of human pluripotent stem cell-derived photoreceptor progenitors in blind mice. Sci Rep. 2016;6:29784.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Jayaram H, Jones MF, Eastlake K, Cottrill PB, Becker S, Wiseman J, Khaw PT, Limb GA. Transplantation of photoreceptors derived from human müller glia restore rod function in the P23H Rat. Stem Cells Transl Med. 2014;3(3):323–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Coles BLK, Angenieux B, Inoue T, Del Rio-Tsonis K, Spence JR, McInnes RR, Arsenijevic Y, van der Kooy D. Facile isolation and the characterization of human retinal stem cells. Proc Natl Acad Sci. 2004;101(44):15772–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Ballios BG, Clarke L, Coles BLK, Shoichet MS, Van Der Kooy D. The adult retinal stem cell is a rare cell in the ciliary epithelium whose progeny can differentiate into photoreceptors. Biol Open. 2012;1(3):237–46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Inoue T, Coles BLK, Dorval K, Bremner R, Bessho Y, Kageyama R, Hino S, Matsuoka M, Craft CM, Mclnnes RR, Temblay F, Prusky GT, van der Kooy D. Maximizing functional photoreceptor differentiation from adult human retinal stem cells. Stem Cells. 2010;28(3):489–500.

    PubMed  PubMed Central  CAS  Google Scholar 

  76. Tropepe V, Coles BL, Chiasson BJ, Horsford DJ, Elia AJ, McInnes RR, van der Kooy D. Retinal stem cells in the adult mammalian eye. Science. 2000;287(5460):2032–6.

    Article  PubMed  CAS  Google Scholar 

  77. Turner DL, Cepko CL. A common progenitor for neurons and glia persists in rat retina late in development. Nature. 1987;328(6126):131–6.

    Article  PubMed  CAS  Google Scholar 

  78. Das AV, Mallya KB, Zhao X, Ahmad F, Bhattacharya S, Thoreson WB, Hegde GV, Ahmad I. Neural stem cell properties of Müller glia in the mammalian retina: Regulation by Notch and Wnt signaling. Dev Biol. 2006;299(1):283–302.

    Article  PubMed  CAS  Google Scholar 

  79. Lawrence JM, Singhal S, Bhatia B, Keegan DJ, Reh TA, Luthert PJ, Khaw PT, Limb GA. MIO-M1 cells and similar müller glial cell lines derived from adult human retina exhibit neural stem cell characteristics. Stem Cells. 2007;25(8):2033–43.

    Article  PubMed  CAS  Google Scholar 

  80. MacNeil A, Pearson RA, MacLaren RE, Smith AJ, Sowden JC, Ali RR. Comparative analysis of progenitor cells isolated from the iris, pars plana, and ciliary body of the adult porcine eye. Stem Cells. 2007;25(10):2430–8.

    Article  PubMed  Google Scholar 

  81. Bhatia B, Singhal S, Lawrence JM, Khaw PT, Limb GA. Distribution of Müller stem cells within the neural retina: Evidence for the existence of a ciliary margin-like zone in the adult human eye. Exp Eye Res. 2009;89(3):373–82.

    Article  PubMed  CAS  Google Scholar 

  82. Gualdoni S, Baron M, Lakowski J, Decembrini S, Smith AJ, Pearson RA, Ali RR, Sowden JC. Adult ciliary epithelial cells, previously identified as retinal stem cells with potential for retinal repair, fail to differentiate into new rod photoreceptors. Stem Cells. 2010;28(6):1048–59.

    Article  PubMed  CAS  Google Scholar 

  83. Osakada F, Ikeda H, Sasai Y, Takahashi M. Stepwise differentiation of pluripotent stem cells into retinal cells. Nat Protoc. 2009;4(6):811–24.

    Article  PubMed  CAS  Google Scholar 

  84. Osakada F, Ikeda H, Mandai M, Wataya T, Watanabe K, Yoshimura N, Akaike A, Sasai Y, Takahashi M, Takahashi M. Toward the generation of rod and cone photoreceptors from mouse, monkey and human embryonic stem cells. Nat Biotechnol. 2008;26(2):215–24.

    Article  PubMed  CAS  Google Scholar 

  85. Lamba DA, Gust J, Reh TA. Transplantation of human embryonic stem cell-derived photoreceptors restores some visual function in CRX-deficient mice. Cell Stem Cell. 2009;4(1):73–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Homma K, Okamoto S, Mandai M, Gotoh N, Rajasimha HK, Chang Y-S, Chen S, Li W, Cogliati T, Swaroop A, Takahashi M. Developing rods transplanted into the degenerating retina of CRX-knockout mice exhibit neural activity similar to native photoreceptors. Stem Cells. 2013;31(6):1149–59.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Gust J, Reh TA. Adult donor rod photoreceptors integrate into the mature mouse retina. Investig Opthalmol Vis Sci. 2011;52(8):5266.

    Article  Google Scholar 

  88. Salero E, Blenkinsop TA, Corneo B, Harris A, Rabin D, Stern JH, Temple S. Adult human RPE can be activated into a multipotent stem cell that produces mesenchymal derivatives. Cell Stem Cell. 2012;10(1):88–95.

    Article  PubMed  CAS  Google Scholar 

  89. Zhu D, Deng X, Spee C, Sonoda S, Hsieh C-L, Barron E, Pera M, Hinton DR. Polarized secretion of PEDF from human embryonic stem cell–derived rpe promotes retinal progenitor cell survival. Investig Opthalmol Vis Sci. 2011;52(3):1573.

    Article  CAS  Google Scholar 

  90. Castanheira P, Torquetti L, Nehemy MB, Goes AM. Retinal incorporation and differentiation of mesenchymal stem cells intravitreally injected in the injured retina of rats. Arq Bras Oftalmol. 2008;71(5):644–50.

    Article  PubMed  Google Scholar 

  91. Luo YHL, da Cruz L. The argus II retinal prosthesis system. Prog Retin Eye Res. 2016;50:89–107.

    Article  PubMed  Google Scholar 

  92. Humayun MS, Dorn JD, Da Cruz L, Dagnelie G, Sahel JA, Stanga PE, et al. Interim results from the international trial of second sight’s visual prosthesis. Ophthalmology. 2012;119(4):779–88.

    Article  PubMed  Google Scholar 

  93. Stanga PE Jr, Sahel JA, da Cruz L, Hafezi F, Merlini F, Coley B, et al. Patients blinded by outer retinal dystrophies are able to perceive simultaneous colors using the argus II retinal prosthesis system. Invest Ophthalmol Vis Sci. 2012;53(14):6952.

    Google Scholar 

  94. Stanga PE, Hafezi F, Sahel JA, da Cruz L, Merlini F, Coley B, et al. Patients blinded by outer retinal dystrophies are able to perceive color using the argustm ii retinal prosthesis system. Invest Ophthalmol Vis Sci. 2011;52(14):4949.

    Google Scholar 

  95. da Cruz L, Dorn JD, Humayun MS, Dagnelie G, Handa J, Barale P-O, et al. Five-year safety and performance results from the Argus II retinal prosthesis system clinical trial. Ophthalmology. 2016;123(10):2248–54.

    Article  PubMed  Google Scholar 

  96. Stingl K, Bartz-Schmidt KU, Besch D, Chee CK, Cottriall CL, Gekeler F, et al. Subretinal visual implant Alpha IMS—clinical trial interim report. Vis Res. 2015;111(Pt B):149–60.

    Article  PubMed  Google Scholar 

  97. Ho AC, Humayun MS, Dorn JD, Da Cruz L, Dagnelie G, Handa J, et al. Long-term results from an epiretinal prosthesis to restore sight to the blind. Ophthalmology. 2015;122(8):1547–54.

    Article  PubMed  Google Scholar 

  98. Kim H, Kim JS. A guide to genome engineering with programmable nucleases. Nat Rev Genet. 2014;15(5):321–34.

    Article  PubMed  CAS  Google Scholar 

  99. Bibikova M, Beumer K, Trautman JK, Carroll D. Enhancing gene targeting with designed zinc finger nucleases. Science. 2003;300(5620):764.

    Article  PubMed  CAS  Google Scholar 

  100. Fishman-Lobell J, Rudin N, Haber JE. Two alternative pathways of double-strand break repair that are kinetically separable and independently modulated. Mol Cell Biol. 1992;12(3):1292–303.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Rouet P, Smih F, Jasin M. Expression of a site-specific endonuclease stimulates homologous recombination in mammalian cells. Proc Natl Acad Sci U S A. 1994;91(13):6064–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Cho SW, Kim S, Kim JM, Kim JS. Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat Biotechnol. 2013;31(3):230–2.

    Article  PubMed  CAS  Google Scholar 

  103. Hou Z, Zhang Y, Propson NE, Howden SE, Chu LF, Sontheimer EJ, et al. Efficient genome engineering in human pluripotent stem cells using Cas9 from Neisseria meningitidis. Proc Natl Acad Sci U S A. 2013;110(39):15644–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Hwang WY, Fu Y, Reyon D, Maeder ML, Tsai SQ, Sander JD, et al. Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol. 2013;31(3):227–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Swiech L, Heidenreich M, Banerjee A, Habib N, Li Y, Trombetta J, et al. In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9. Nat Biotechnol. 2015;33(1):102–6.

    Article  PubMed  CAS  Google Scholar 

  106. Ran FA, Cong L, Yan WX, Scott DA, Gootenberg JS, Kriz AJ, et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature. 2015;520(7546):186–91.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. Hung SS, Chrysostomou V, Li F, Lim JK, Wang JH, Powell JE, et al. AAV-mediated CRISPR/Cas Gene editing of retinal cells in vivo. Invest Ophthalmol Vis Sci. 2016;57(7):3470–6.

    Article  PubMed  CAS  Google Scholar 

  108. Yiu G, Tieu E, Nguyen AT, Wong B, Smit-McBride Z. Genomic disruption of VEGF-A expression in human retinal pigment epithelial cells using CRISPR-Cas9 endonuclease. Invest Ophthalmol Vis Sci. 2016;57(13):5490–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Koo T, Lee J, Kim JS. Measuring and reducing off-target activities of programmable nucleases including CRISPR–Cas9. Mol Cell. 2015;38:475–81.

    Article  CAS  Google Scholar 

  110. Iyer V, et al. Off-target mutations are rare in Cas9-modified mice. Nat Methods. 2015;12:479.

    Article  PubMed  CAS  Google Scholar 

  111. Schaefer KA, Wu WH, Colgan DF, Tsang SH, Bassuk AG, Mahajan VB. Unexpected mutations after CRISPR-Cas9 editing in vivo. Nat Methods. 2017;14(6):547–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Burnight ER, Gupta M, Wiley LA, Anfinson KR, Tran A, Triboulet R, Hoffmann JM, Klaahsen DL, Andorf JL, Jiao C, Sohn EH, Adur MK, Ross JW, Mullins RF, Daley GQ, Schlaeger TM, Stone EM, Tucker BA. Using CRISPR-Cas9 to generate gene-corrected autologous iPSCs for the treatment of inherited retinal degeneration. Mol Ther. 2017;25(9):1999–2013.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Amirfarbod Yazdanyar M.D., Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Moshiri, A., Yazdanyar, A. (2018). Inherited Retinal Diseases. In: Yiu, G. (eds) Vitreoretinal Disorders. Current Practices in Ophthalmology. Springer, Singapore. https://doi.org/10.1007/978-981-10-8545-1_5

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-8545-1_5

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-8544-4

  • Online ISBN: 978-981-10-8545-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics