Current Pharmacological Concepts in the Treatment of the Retinitis Pigmentosa

  • Xiu-Feng Huang
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1074)


Retinitis pigmentosa (RP) encompasses a heterogeneous group of inherited retinal disorders characterized by progressive photoreceptor and/or retinal pigment epithelial (RPE) degenerations with a prevalence approximately 1 in 4000 in the general population. Over 70 causative genes have been defined in RP families, and a number of animal models have been identified so far. However there have been no widely recognized treatments able to recover or reverse the degenerating retina, to prevent the disease deterioration, ultimately to restore the remaining vision. Therapeutics advancements have been achieved including gene therapy, pharmacotherapy, cell replacement, neurotrophic factors, and retinal prosthesis. In this review, we focus on the pharmaceutical drugs for RP with emphases on the context of drug discovery, development, and clinical translation.


Retinitis pigmentosa Pharmacotherapy Treatment Vitamin A Lutein Docosahexaenoic acid Valproic acid Neurotrophic factor and growth factor 


  1. Bahrami H, Melia M, Dagnelie G (2006) Lutein supplementation in retinitis pigmentosa: PC-based vision assessment in a randomized double-masked placebo-controlled clinical trial [NCT00029289]. BMC Ophthalmol 6:23CrossRefGoogle Scholar
  2. Berson EL (1982) Nutrition and retinal degenerations. Vitamin A, taurine, ornithine, and phytanic acid. Retina 2(4):236–255CrossRefGoogle Scholar
  3. Berson EL, Rosner B, Sandberg MA, Hayes KC, Nicholson BW, Weigel-DiFranco C, Willett W (1993) A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol 111(6):761–772CrossRefGoogle Scholar
  4. Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Brockhurst RJ, Hayes KC, Johnson EJ, Anderson EJ, Johnson CA, Gaudio AR et al (2010) Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol 128(4):403–411CrossRefGoogle Scholar
  5. Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Moser A, Brockhurst RJ, Hayes KC, Johnson CA, Anderson EJ, Gaudio AR et al (2004a) Clinical trial of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment. Arch Ophthalmol 122(9):1297–1305CrossRefGoogle Scholar
  6. Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Moser A, Brockhurst RJ, Hayes KC, Johnson CA, Anderson EJ, Gaudio AR et al (2004b) Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment: subgroup analyses. Arch Ophthalmol 122(9):1306–1314CrossRefGoogle Scholar
  7. Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Willett WC (2012) Omega-3 intake and visual acuity in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol 130(6):707–711CrossRefGoogle Scholar
  8. Biermann J, Grieshaber P, Goebel U, Martin G, Thanos S, Di Giovanni S, Lagreze WA (2010) Valproic acid-mediated neuroprotection and regeneration in injured retinal ganglion cells. Invest Ophthalmol Vis Sci 51(1):526–534CrossRefGoogle Scholar
  9. Clemson CM, Tzekov R, Krebs M, Checchi JM, Bigelow C, Kaushal S (2011) Therapeutic potential of valproic acid for retinitis pigmentosa. Br J Ophthalmol 95(1):89–93CrossRefGoogle Scholar
  10. Del Rio P, Irmler M, Arango-Gonzalez B, Favor J, Bobe C, Bartsch U, Vecino E, Beckers J, Hauck SM, Ueffing M (2011) GDNF-induced osteopontin from Muller glial cells promotes photoreceptor survival in the Pde6brd1 mouse model of retinal degeneration. Glia 59(5):821–832CrossRefGoogle Scholar
  11. Faktorovich EG, Steinberg RH, Yasumura D, Matthes MT, LaVail MM (1990) Photoreceptor degeneration in inherited retinal dystrophy delayed by basic fibroblast growth factor. Nature 347(6288):83–86CrossRefGoogle Scholar
  12. Frasson M, Picaud S, Leveillard T, Simonutti M, Mohand-Said S, Dreyfus H, Hicks D, Sabel J (1999) Glial cell line-derived neurotrophic factor induces histologic and functional protection of rod photoreceptors in the rd/rd mouse. Invest Ophthalmol Vis Sci 40(11):2724–2734PubMedGoogle Scholar
  13. German OL, Insua MF, Gentili C, Rotstein NP, Politi LE (2006) Docosahexaenoic acid prevents apoptosis of retina photoreceptors by activating the ERK/MAPK pathway. J Neurochem 98(5):1507–1520CrossRefGoogle Scholar
  14. Gottlicher M, Minucci S, Zhu P, Kramer OH, Schimpf A, Giavara S, Sleeman JP, Lo Coco F, Nervi C, Pelicci PG et al (2001) Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J 20(24):6969–6978CrossRefGoogle Scholar
  15. Hamel C (2006) Retinitis pigmentosa. Orphanet J Rare Dis 1:40CrossRefGoogle Scholar
  16. Hartong DT, Berson EL, Dryja TP (2006) Retinitis pigmentosa. Lancet 368:1795–1809CrossRefGoogle Scholar
  17. Hoffman DR, Locke KG, Wheaton DH, Fish GE, Spencer R, Birch DG (2004) A randomized, placebo-controlled clinical trial of docosahexaenoic acid supplementation for X-linked retinitis pigmentosa. Am J Ophthalmol 137(4):704–718PubMedGoogle Scholar
  18. Kubota A, Nishida K, Nakashima K, Tano Y (2006) Conversion of mammalian Muller glial cells into a neuronal lineage by in vitro aggregate-culture. Biochem Biophys Res Commun 351(2):514–520CrossRefGoogle Scholar
  19. Liang FQ, Aleman TS, Dejneka NS, Dudus L, Fisher KJ, Maguire AM, Jacobson SG, Bennett J (2001) Long-term protection of retinal structure but not function using RAAV.CNTF in animal models of retinitis pigmentosa. Mol Ther 4(5):461–472CrossRefGoogle Scholar
  20. Maeda A, Maeda T, Palczewski K (2006) Improvement in rod and cone function in mouse model of fundus albipunctatus after pharmacologic treatment with 9-cis-retinal. Invest Ophthalmol Vis Sci 47(10):4540–4546CrossRefGoogle Scholar
  21. Marmor MF (1993) A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol 111(11):1460–1461; author reply 1463–5CrossRefGoogle Scholar
  22. Massof RW, Fishman GA (2010) How strong is the evidence that nutritional supplements slow the progression of retinitis pigmentosa? Arch Ophthalmol 128(4):493–495CrossRefGoogle Scholar
  23. Mizota A, Sato E, Taniai M, Adachi-Usami E, Nishikawa M (2001) Protective effects of dietary docosahexaenoic acid against kainate-induced retinal degeneration in rats. Invest Ophthalmol Vis Sci 42(1):216–221PubMedGoogle Scholar
  24. Nguyen CT, Vingrys AJ, Bui BV (2008) Dietary omega-3 fatty acids and ganglion cell function. Invest Ophthalmol Vis Sci 49(8):3586–3594CrossRefGoogle Scholar
  25. Radu RA, Yuan Q, Hu J, Peng JH, Lloyd M, Nusinowitz S, Bok D, Travis GH (2008) Accelerated accumulation of lipofuscin pigments in the RPE of a mouse model for ABCA4-mediated retinal dystrophies following Vitamin A supplementation. Invest Ophthalmol Vis Sci 49(9):3821–3829CrossRefGoogle Scholar
  26. Rotenstreich Y, Harats D, Shaish A, Pras E, Belkin M (2010) Treatment of a retinal dystrophy, fundus albipunctatus, with oral 9-cis-{beta}-carotene. Br J Ophthalmol 94(5):616–621CrossRefGoogle Scholar
  27. Rotstein NP, Aveldano MI, Barrantes FJ, Roccamo AM, Politi LE (1997) Apoptosis of retinal photoreceptors during development in vitro: protective effect of docosahexaenoic acid. J Neurochem 69(2):504–513CrossRefGoogle Scholar
  28. Sahni JN, Angi M, Irigoyen C, Semeraro F, Romano MR, Parmeggiani F (2011) Therapeutic challenges to retinitis pigmentosa, from neuroprotection to gene therapy. Curr Genomics 12(4):276–284CrossRefGoogle Scholar
  29. Sandberg MA, Rosner B, Weigel-DiFranco C, Berson EL (2011) Lack of scientific rationale for use of valproic acid for retinitis pigmentosa. Br J Ophthalmol 95(5):744CrossRefGoogle Scholar
  30. Semba RD, Dagnelie G (2003) Are lutein and zeaxanthin conditionally essential nutrients for eye health? Med Hypotheses 61(4):465–472CrossRefGoogle Scholar
  31. Shintani K, Shechtman DL, Gurwood AS (2009) Review and update: current treatment trends for patients with retinitis pigmentosa. Optometry 80(7):384–401CrossRefGoogle Scholar
  32. Sibulesky L, Hayes KC, Pronczuk A, Weigel-DiFranco C, Rosner B, Berson EL (1999) Safety of <7500 RE (<25000 IU) vitamin A daily in adults with retinitis pigmentosa. Am J Clin Nutr 69(4):656–663CrossRefGoogle Scholar
  33. Sieving PA, Caruso RC, Tao W, Coleman HR, Thompson DJ, Fullmer KR, Bush RA (2006) Ciliary neurotrophic factor (CNTF) for human retinal degeneration: phase I trial of CNTF delivered by encapsulated cell intraocular implants. Proc Natl Acad Sci U S A 103(10):3896–3901CrossRefGoogle Scholar
  34. Sisk RA (2012) Valproic acid treatment may be harmful in non-dominant forms of retinitis pigmentosa. Br J Ophthalmol 96(8):1154–1155CrossRefGoogle Scholar
  35. Talcott KE, Ratnam K, Sundquist SM, Lucero AS, Lujan BJ, Tao W, Porco TC, Roorda A, Duncan JL (2011) Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic factor treatment. Invest Ophthalmol Vis Sci 52(5):2219–2226CrossRefGoogle Scholar
  36. Tao W, Wen R, Goddard MB, Sherman SD, O'Rourke PJ, Stabila PF, Bell WJ, Dean BJ, Kauper KA, Budz VA et al (2002) Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa. Invest Ophthalmol Vis Sci 43(10):3292–3298PubMedGoogle Scholar
  37. Uteza Y, Rouillot JS, Kobetz A, Marchant D, Pecqueur S, Arnaud E, Prats H, Honiger J, Dufier JL, Abitbol M et al (1999) 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 U S A 96(6):3126–3131CrossRefGoogle Scholar
  38. van Schooneveld MJ, van den Born LI, van Genderen M, Bollemeijer JG (2011) The conclusions of Clemson et al concerning valproic acid are premature. Br J Ophthalmol 95(1):153; author reply 153–4Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Xiu-Feng Huang
    • 1
  1. 1.The Eye Hospital of Wenzhou Medical University, The State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of HealthWenzhouChina

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