Stargardt ve Fundus Flavimaculatus; Güncel Tedavi ve Geliştirilmekte olanTedaviler

Çağatay ÇAĞLAR (Hitit Üniversitesi Tıp Fakültesi, Göz Hastalıkları Ana Bilim Dalı, Çorum, Türkiye)
Güncel Retina Dergisi
94 0
Yıl: 2021 Cilt: 5 Sayı: 2 Sayfa Aralığı: 190 - 200 Metin Dili: Türkçe İndeks Tarihi: 08-06-2021

Stargardt ve Fundus Flavimaculatus; Güncel Tedavi ve Geliştirilmekte olanTedaviler

Öz:
Stargardt maküler distrofisi etkin bir tedavisi olmayan herediter bir retina dejenerasyonudur. Hastalığının patofizyolojisi halen tam olarak anlaşılamamıştır. Şu an mevcut bir tedavisi olmasa da, tedavideki ihtiyacı karşılamak için birçok kategoride araştırmalar devam etmektedir. Bunlar görsel siklus inhibitörleri, kompleman inhibitörleri, ABCA4 gen terapisi, retina pigment epitel kaynaklı kök hücrenin subretinal transplantasyonudur. İnsanlarda etkin ve güvenli olarak değerlendirilebilecek bir tedavi için daha ileri çalışmalara ihtiyaç vardır. Bu derlemede Stargardt hastalığı için araştırılan tedaviler anlatılmıştır.
Anahtar Kelime:

Stargardt and Fundus Flavimaculatus; Current and Developing Treatments

Öz:
Stargardt macular dystrophy is a hereditary retinal degeneration that lacks effective treatment options. The pathophysiology of disease is still not fully understood. While there are currently no available treatments for Stargardt disease, there are many categories of therapeutics under investigation to fulfill this unmet need for treatment. These include investigational visualcycle modulators, complement inhibitors, ABCA4 gene therapy, and subretinal transplantation of stem cell derived retina pigment epitel cells. Further trials are warranted to assess efficacy and safety in humans. In this review, the treatments inves tigated for the Stargardt disease are explained.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Derleme Erişim Türü: Bibliyografik
  • Michaelides M, Hunt DM, Moore AT. The genetics of inherited macular dystrophies. J Med Genet. 2003;40(9):641–650.
  • Stone EM, Andorf JL, Whitmore SS, DeLuca AP, Giacalone JC , Streb LM, et al. Clinically focused molecular investigation of 1000 consecutive families with inherited retinal disease. Ophthalmology 2017;124(9):1314–1331.
  • Allikmets R, Shroyer NF, Singh N, Lewis RA, Bernstein PS, Peiffer A, et al. Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science 1997;277(5333):1805–1807.
  • Allikmets R, Singh N, Sun H, Shroyer NF, Hutchinson A, Chidambaram A, et al. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat Genet. 1997;15(3):236–246.
  • Yi J, Li S, Jia X, Xiao X, Wang P, Guo X, et al. Evaluation of the ELOVL4, PRPH2 and ABCA4 genes in patients with Stargardt macular degeneration. Mol Med Rep. 2012;6(5):1045–1049.
  • Ng KP, Gugiu B, Renganathan K, Davies MW, Gu X, Crabb JS, et al. Retinal pigment epithelium lipofuscin proteomics. Mol Cell Proteomics. 2008;7(7):1397–1405.
  • Zernant J, Xie YA, Ayuso C, Riveiro-Alvarez R, Lopez-Martinez MA, Simonelli F, et al. Analysis of the ABCA4 genomic locus in Stargardt disease. Hum Mol Genet. 2014;23(25):6797–6806.
  • 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;703:105–125.
  • Menteş J. Stargardt Hastalığı ve Fundus Flavimaculatus. Turkiye Klinikleri J Ophthalmol-Özel sayı 2009;2(1):20-26.
  • Sparrow JR, Gregory-Roberts E, Yamamoto K, Blonska A, Ghosh SK, Ueda K, et al. The bisretinoids of retinal pigment epithelium. Prog Retin Eye Res. 2012;31(2):121–135.
  • Sparrow JR, Boulton M. RPE lipofuscin and its role in retinal pathobiology. Exp Eye Res. 2005;80(5):595–606.
  • Hussain RM, Gregori NZ, Ciulla TA, Lam BL. Pharmacotherapy of retinal disease with visual cycle modulators. Expert Opin Pharmacother. 2018;19(5):471–481.
  • Röck T, Schatz A, Naycheva L, Gosheva M, Pach J, Wilhelm B, et al. Effects of transcorneal electrical stimulation in patients with Stargardt’s disease. Ophthalmologe 2013;110(1):68–73.
  • Kondrot EC. Improvement in vision parameters for participants treated with alternative therapies in a 3-day program. Altern Ther Health Med. 2015;21(6):22–35.
  • Teussink MM, Lee MD, Smith RT, Van Huet RA, Klaver CC, Klevering BJ, et al. The effect of light deprivation in patients with Stargardt disease. Am J Ophthalmol. 2015;159(5):964–972.
  • Tanna P, Strauss RW, Fujinami K, Michaelides M. Stargardt disease: clinical features, molecular genetics, animal models and therapeutic options. Br J Ophthalmol. 2017;101(1):25–30.
  • Kaufman Y, Ma L, Washington I. Deuterium enrichment of vitamin A at the C20 position slows the formation of detrimental vitamin A dimers in wild-type rodents. J Biol Chem. 2011;286(10):7958–7965.
  • Mihai DM, Jiang H, Blaner WS, Romanov A, Washington I. The retina rapidly incorporates ingested C20-D(3)-vitamin A in a swine model. Mol Vis. 2013;19:1677–1683.
  • Lem J, Fain GL. Constitutive opsin signaling: night blindness or retinal degeneration? Trends Mol Med. 2004;10(4):150–157.
  • Baehr W, Wu SM, Bird AC, Palczewski K. The retinoid cycle and retina disease. Vis Res. 2003;43(28):2957–2958.
  • Ma L, Kaufman Y, Zhang J, Washington I. C20-D3-vitamin A slows lipofuscin accumulation and electrophysiological retinal degeneration in a mouse model of Stargardt disease. J Biol Chem. 2011;286(10):7966-7974. Issa PC, Barnard AR, Herrmann P, Washington I, MacLaren RE. Rescue of the Stargardt phenotype in Abca4 knockout mice through inhibition of vitamin A dimerization. Proc Natl Acad Sci USA. 2015;112(27):8415–8420.
  • Kiser PD, Zhang J, Badiee M, Li Q, Shi W, Sui X, et al. Catalytic mechanism of a retinoid isomerase essential for vertebrate vision. Nat Chem Biol. 2015;11(6):409–415.
  • Zhang J, Kiser PD, Badiee M, Palczewska G, Dong Z, Golczak M, et al. Molecular pharmacodynamics of emixustat in protection against retinal degeneration. J Clin Invest. 2015;125(7):2781–2794.
  • Kubota R, Boman NL, David R, Mallikaarjun S, Patil S, Birch D. et al. Safety and effect on rod function of ACU-4429, a novel small-molecule visual cycle modulator. Retina 2012;32(1):183–188.
  • Dugel PU, Novack RL, Csaky KG, Richmond PP, Birch DG, Kubota R. Phase II, randomized, placebo-controlled, 90-day study of emixustat hydrochloride in geographic atrophy associated with dry age-related macular degeneration. Retina 2015;35(6):1173–1183.
  • Rosenfeld PJ, Dugel PU, Holz FG, Heier JS, Pearlman JA, Novack RL, et al. Emixustat Hydrochloride for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Clinical Trial. Ophthalmology 2018;125(10):1556-1567.
  • Malpeli G, Folli C, Berni R. Retinoid binding to retinolbinding protein and the interference with the interaction with transthyretin. Biochim Biophys Acta. 1996;1294(1):48–54.
  • Radu RA, Han Y, Bui TV, Nusinowitz S, Bok D, Lichter J, et al. Reductions in serum vitamin A arrest accumulation of toxic retinal fluorophores: a potential therapy for treatment of lipofuscin-based retinal diseases. Invest Ophthalmol Vis Sci. 2005;46(12):4393–4401.
  • Mata NL, Lichter JB, Vogel R, Han Y, Bui TV, Singerman LJ, et al. Investigation of oral fenretinide for treatment of geographic atrophy in age-related macular degeneration. Retina 2013;33(3):498–507.
  • Samuel W, Kutty RK, Nagineni S, Vijayasarathy C, Chandraratna RAS, Wiggert B. N-(4-hydroxyphenyl)retinamide induces apoptosis in human retinal pigment epithelial cells: retinoic acid receptors regulate apoptosis, reactive oxygen species generation, and the expression of heme oxygenase-1 and Gadd153. J Cell Physiol. 2006;209(3):854–865.
  • Turton JA, Willars GB, Haselden JN, Ward SJ, Steele CE, Hicks RM. Comparative teratogenicityof nine retinoids in the rat. Int J Exp Pathol. 1992;73(5):551–563.
  • Cohen SM, Storer RD, Criswell KA, Doerrer NG, Dellarco VL, Pegg DG, et al. Hemangiosarcoma in rodents: mode-ofaction evaluation and human relevance. Toxicol Sci. 2009;111(1):4–18.
  • Motani A, Wang Z, Conn M, Siegler K, Zhang Y, Liu Q, Johnstone S, et al. Identification and characterization of a nonretinoid ligand for retinol-binding protein 4 which lowers serum retinol-binding protein 4 levels in vivo. J Biol Chem. 2009;284(12):7673–7680.
  • Dobri N, Qin Q, Kong J, Yamamoto K, Liu Z, Moiseyev G, 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(1):85–95.
  • Hussain RM, Ciulla TA, Berrocal AM, Gregori NZ, Flynn HW, Lam BL. Stargardt macular dystrophy and evolving therapies. Expert Opin Biol Ther. 2018;10:1049-1059.
  • Maeda A, Golczak M, Chen Y, Okano K, Kohno H, Shiose S. Primary amines protect against retinal degeneration in mouse models of retinopathies. Nat Chem Biol. 2011;8(2):170-178.
  • Radu RA, Mata NL, Nusinowitz S, Liu X, Sieving PA, Travis GH, et al. Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt’s macular degeneration. Proc Natl Acad Sci USA. 2003;100(8):4742–4747.
  • Weleber RG, Denman ST, Hanifin JM, Cunningham WJ. Abnormal retinal function associated with isotretinoin therapy for acne. Arch Ophthalmol. 1986;10(6)4:831–837.
  • Sieving PA, Chaudhry P, Kondo M, Provenzano M, Wu D, Carlson TJ, et al. Inhibition of the visual cycle in vivo by 13-cis retinoic acid protects from light damage and provides a mechanism for night blindness in isotretinoin therapy. Proc Natl Acad Sci USA. 2001;98(4):1835–1840.
  • Battaglia PM, La Spina C, Corradetti G, Berchicci L, Petruzzi G, Bandello F. Retinal hereditary and degenerative/dystrophic diseases (non-age-related macular degeneration. Dev Ophthalmol. 2016;55:205–211.
  • Zhou J, Kim SR, Westlund BS, Sparrow JR. Complement activation bybisretinoid constituents of RPE lipofuscin. Invest Ophthalmol Vis Sci. 2009;50(3):1392–1399.
  • Zhou J, Jang YP, Kim SR, Sparrow JR. Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium. Proc Natl Acad Sci USA. 2006;103(44):16182–16187.
  • Berchuck JE, Yang P, Toimil BA, Ma Z, Baciu P, Jaffe GJ. All-trans-retinal sensitizes human RPE cells to alternative complement pathway-induced cell death. Invest Ophthalmol Vis Sci. 2013;54(4):2669–2677.
  • Radu RA, Hu J, Yuan Q, Welch DL, Makshanoff J, Lloyd M, et al. Complement system dysregulation and inflammation in the retinal pigment epithelium of a Mouse model for Stargardt macular degeneration. J Biol Chem. 2011;286(21):18593–18601.
  • Lenis TL, Sarfare S, Jiang Z, Lloyd MB, Bok D, Radu RA, et al. Complement modulation in the retinal pigment epithelium rescues photoreceptor degeneration in a mouse model of Stargardt disease. Proc Natl Acad Sci USA. 2017;114(16):3987–3992.
  • Kassa E, Ciulla TA, Hussain RM, Dugel PU. Complement Inhibition as a Therapeutic Strategy in Retinal Disorders Expert Opin Biol Ther. 2019;19(4):335-342.
  • Csaky KG. Complement C5 inhibition as a potential treatment for autosomal recessive stargardt disease (STGD1): design of a clinical trial assessing a novel treatment and primary outcome measure. Invest Ophthalmol Vis Sci 2018;59(9):1569.
  • Zhou JH, Rossi J. Aptamers as targeted therapeutics: current potential and challenges. Nat Rev Drug Discov. 2017;16(3):181-202.
  • Issa CP, Barnard AR, Singh MS, Carter E, Jiang Z, Radu RA, et al. Fundus autofluorescence in the Abca4(-/-) mouse model of Stargardt disease— correlation with accumulation of A2E, retinal function, and histology. Invest Ophthalmol Vis Sci. 2013;54(7):5602–5612.
  • Schraermeyer U, Peters S, Thumann G, Kociok N, Heimann K. Melanin granules of retinal pigment epithelium are connected with the lysosomal degradation pathway. Exp Eye Res. 1999;68(2):237–245.
  • Julien S, Schraermeyer U. Lipofuscin can be eliminated from the retinal pigment epithelium of monkeys. Neurobiol Aging. 2012(4);33:2390–2397.
  • Fang Y, Tschulakow A, Tikhonovich M, Taubitz T, Illing B, Schultheiss A, et al. Preclinical results of a new pharmacological therapy approach for Stargardt disease and dry age-related macular degeneration. ARVO E-Abstract. 2017;B0287.
  • Logan S, Anderson RE. Dominant Stargardt Macular Dystrophy (STGD3) and ELOVL4. Adv Exp Med Biol. 2014;801:447–453. 55. Bernstein PS, Tammur J, Singh N, Hutchinson A, Dixon M, Pappas CM, et al. Diverse macular dystrophy phenotype caused by a novel complex mutation in the ELOVL4 gene. Invest Ophthalmol Vis Sci. 2001;42(13):3331–3336.
  • Choi R, Gorusupudi A, Bernstein PS. Long-term follow-up of autosomal dominant Stargardt macular dystrophy (STGD3) subjects enrolled in a fish oil supplement interventional trial. Ophthalmic Genet. 2018;39(3):307-313.
  • Aleman TS, Cideciyan AV, Windsor EA, Schwartz SB, Swider M, Chico JD, et al. Macular pigment and lutein supplementation in ABCA4-associated retinal degenerations. Invest Ophthalmol Vis Sci. 2007;48(5):1319–1329.
  • Querques G, Benlian P, Chanu B, Leveziel N, Coscas G, Soubrane G, et al. DHA supplementation for late onset Stargardt disease: NAT-3 study. Clin Ophthalmol. 2010;4(4):575–580.
  • Piccardi M, Fadda A, Martelli F, Marangoni D, Magli A, Minnella AM, et al. Antioxidant Saffron and Central Retinal Function in ABCA4-Related Stargardt Macular Dystrophy. Nutrients 2019;11(10):2461.
  • Mihai, DM, Washington I. Vitamin A dimers trigger the protracted death of retinal pigment epithelium cells. Cell Death Dis. 2014;24(5):e1348.
  • Radu RA, Yuan Q, Hu J, Peng JH, Lloyd M, Nusinowitz S, et al. 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. 2008;49(6):3821–3829.
  • Sofi F, Sodi A, Franco F, Murro V, Biagini D, Miele A, et al. Dietary profile of patients with Stargardt’s disease and Retinitis Pigmentosa: is there a role for a nutritional approach? BMC Ophthalmol. 2016;16:13.
  • Binley K, Widdowson P, Loader J, Kelleher M, Iqball S, Ferrige G, et al. 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):4061–4071.
  • Cicinelli MV, Battista M, Starace V, Parodi MB, Bandello F. Monitoring and Management of the Patient With Stargardt Disease. Clin Optom. 2019;28(11):151-165.
  • Lenis TL, Hu J, Ng SY, Jiang Z, Sarfare S, Lloyd MB, et al. Expression of ABCA4 in the retinal pigment epithelium and its implications for Stargardt macular degeneration. Proc Natl Acad Sci USA. 2018;115(47):E11120–E11127.
  • Sahel JA, Roska B. Gene therapy for blindness. Annu Rev Neurosci. 2013;36:467-488.
  • Acland GM, Aguirre GD, Ray J, Zhang Q, Aleman TS, Cideciyan AV, et al. Gene therapy restores vision in a canine model of childhood blindness. Nat Genet. 2001;28(9):92-95.
  • Trapani I, Puppo A, Auricchio A. Vector platforms for gene therapy of inherited retinopathies. Prog Retin Eye Res. 2014;43(5):108-128.
  • tieger K, Lhériteau E, Moullier P, Rolling F. AAV-mediated gene therapy for retinal disorders inlarge animal models. ILAR J. 2009(10);50:206-224.
  • Le Meur G, Stieger K, Smith AJ, Weber M, Deschamps JY, Nivard D, et al. Restoration of vision in RPE65-deficient Briard dogs using an AAV serotype 4 vector that specifically targets the retinal pigmented epithelium. Gene Ther. 2007;14(2):292-303.
  • Han Z, Conley SM, Naash MI. Gene Therapy for Stargardt Disease Associated With ABCA4 Gene. Adv Exp Med Biol. 2014;801:719-724.
  • Davis JL. The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal Diseases. Am J Ophthalmol. 2018;196:25-29.
  • Warrington KH Jr, Herzog RW. Treatment of human disease by adeno-associated viral gene transfer. Hum Genet. 2006;119(8):571–603.
  • Allocca M, Doria M, Petrillo M, Colella P, Garcia-Hoyos M, Gibbs D, et al. Serotype-dependent packaging of large genes in adeno-associated viral vectors results in effective gene delivery in mice. J Clin Invest. 2008;118(5):1955–1964.
  • Sharif W, Sharif Z. Leber’s congenital amaurosis and the role of gene therapy in congenital retinal disorders. Int J Ophthalmol. 2017;10(3):480–484.
  • Dalkara D, Goureau O, Marazova K, Sahel JA. Let there be light: gene and cell therapy for blindness. Hum Gene Ther 2016(3);27:134–147.
  • Wilson DJ, Sahel JA, Weleber RG, Erker LR, Lauer AK, Stout T, et al. One Year Results of a Phase I/IIa Study of SAR422459 in Patients with Stargardt Macular Degeneration. ARVO Annual Meeting. 2017;58:8.
  • Auricchio A, Trapani I, Allikmets R. Gene therapy of ABCA4-associated diseases. Cold Spring Harb Perspect Med. 2015;5(5):a017301.
  • Han Z, Conley SM, Makkia RS, Cooper MJ, Naash MI. DNA nanoparticle-mediated ABCA4 delivery rescues Stargardt dystrophy in mice. J Clin Invest. 2012;122(9):3221–3226.
  • Han Z, Conley SM, Naash MI. Gene therapy for Stargardt disease associated with ABCA4 gene. Adv Exp Med Biol. 2014;801(12):719–72.
  • Da Sun, Schur RM, Sears AE, Gao SQ, Vaidya A, Sun W, et al. Non-viral Gene Therapy for Stargardt Disease with ECO/pRHO-ABCA4 Self-Assembled Nanoparticles. Ther. 2020;28(1):293–303.
  • Russell S, Bennett J, Wellman JA, Chung DC, Yu ZF, Tillman A, et al. 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):849–860.
  • Ziccardi L, Cordeddu V, Gaddini L, Matteucci A, Parravano M, Malchiodi-Albedi F. Gene Therapy in Retinal Dystrophies. Int J Mol Sci. 2019;20(22):5722.
  • Moore NA, Morral N, Ciulla TA, Bracha P. Gene therapy for inherited retinal and optic nerve degenerations. Expert Opin Biol Ther. 2018;18(1):37–49.
  • Zarbin M. Cell-Based Therapy for Degenerative Retinal Disease. Trends Mol Med. 2016;22(2):115-134.
  • Acar U, Sobacı G. Yakın Gelecek Ne Vaat Ediyor? Biyoteknoloji. Turkiye Klinikleri J Ophthalmol-Özel Sayı. 2015;8(1):125-131.
  • Bennicelli JL, Bennett J. Stem cells set their sights on retinitis pigmentosa. E Life. 2013;2:e01291.
  • Öner A. Retina Hastalıklarında Kök Hücre Tedavisi: Son Gelişmeler. Turk J Ophthalmol 2018;48(1):33-38.
  • Tucker BA, Mullins RF, Stone EM. Stem cells for investigation and treatment of inherited retinal disease. Human Mol Genet. 2014;23(1):9-16.
  • Maeda A, Mandai M, Takahashi M. Gene and Induced Pluripotent Stem Cell Therapy for Retinal Diseases. Annu Rev Genomics Hum Genet. 2019;20(4):201-216.
  • Bracha P, Moore NA, Ciulla TA. Induced pluripotent stem cell-based therapy for age-related macular degeneration. Expert Opin Biol Ther. 2017;17(9):1113–1126.
  • He Y, Zhang Y, Liu X, Ghazaryan E, Li Y, Xie J. Recent Advances of Stem Cell Therapy for Retinitis Pigmentosa. Int J Mol Sci. 2014;15(8):14456-14474.
  • Bharti K, Rao M, Hull SC, Stroncek D, Brooks BP, Feigal E, et al. Developing cellular therapies for retinal degenerative diseases. Invest Ophthalmol Vis Sci2014;55(2):1191-1202.
  • Whiting P, Kerby J, Coffey P, Da Cruz L, McKernan R. Progressing a human embryonic stem-cell-based regenerative medicine therapy towards the clinic. Philos Trans R Soc Lond B Biol Sci. 2015;370(1680):20140375.
  • Ramsden CM, Powner MB, Carr AJ, Smart MJ, Da Cruz L, Coffey PJ. Stem cells in retinal regeneration: past, present and future. Development 2013:140(12):2576-2585.
  • Plaza Reyes A, Petrus-Reurer S, Antonsson L, Stenfelt S, Bartuma H, Panula S et al. Xeno-free and defined human embryonic stem cell-derived retinal pigment epithelial cells functionally integrate in a large-eyed preclinical model. Stem Cell Reports. 2016;6(1):9–17.
  • Carido M, Zhu Y, Postel K, Benkner B, Cimalla P , Karl MO, et al. Characterization of a mouse model with complete RPE loss and its use for RPE cell transplantation. Invest Ophthalmol Vis Sci. 2014;55(8):5431–5444.
  • Lu B, Malcuit C, Wang S, Girman S, Francis P, Lemieux L, et al. Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration. Stem Cells 2009;27(6):2126–2135.
  • Ardeljan D, Chan C-C. Aging is not a disease: distinguishing age-related macular degeneration from aging. Prog Retin Eye Res. 2013;37:68–89.
  • Schwartz SD, Regillo CD, Lam BL, Eliott D, Rosenfeld PJ, Gregori NZ, et al. 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 2015;385(5):509–516.
  • Schwartz SD, Tan G, Hosseini H, Nagiel A. Subretinal transplantation of embryonic stem cell-derived retinal pigment epithelium for the treatment of macular degeneration: an assessment at 4 years. Invest Ophthalmol Vis Sci. 2016;57(5):1-9.
  • Gregori N, Schwartz S, Regillo C, Lam B, Eliott D, Rosenfeld P, et al. PA096 Long-term outcomes of human embryonic stem cell–derived retinal pigment epithelial cell transplantation for retinal degeneration from 2 phase 1/2 trials. AAO Annual Meeting, New Orleans, LA, 2017.
  • Song WK, Park KM, Kim HJ, Lee JH, Choi J, Chong SY, et al. Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: preliminary results in Asian patients. Stem Cell Reports. 2015;4(4):860-872.
  • Emre E, Yüksel N, Duruksu G, Pirhan D, Subaşi C, Erman G. Neuroprotective effects of intravitreally transplanted adipose tissue and bone marrow-derived mesenchymal stem cells in an experimental ocular hypertension model. Cytotherapy. 2015;17(3):543-559.
  • Jian Q, Li Y, Yin ZQ. Rat BMSCs initiate retinal endogenous repair through NGF/TrkA signaling. Exp Eye Res. 2015;132(1):34-47.
  • Leung EH, Flynn HW, Albini TA, Medina CA. Retinal detachment after subretinal stem cell transplantation. Ophthalmic Surg Lasers Imaging Retina 2016;47(6):600–601.
  • Weiss JN, Levy S, Malkin A. Stem Cell Ophthalmology Treatment Study (SCOTS) for retinal and optic nerve diseases: a preliminary report. Neural Regen Res. 2015;10(6):982-988.
  • Weiss JN, Levy S, Benes SC. Stem Cell Ophthalmology Treatment Study (SCOTS) for retinal and optic nerve diseases: a case report of improvement in relapsing auto-immune optic neuropathy. Neural Regen Res. 2015;10(9):1507-1515.
  • Weiss JN, Benes SC, Levy S. Stem Cell Ophthalmology Treatment Study (SCOTS): improvement in serpiginous choroidopathy following autologous bone marrow derived stem cell treatment. Neural Regen Res. 2016;11(9):1512-1516.
  • Weiss JN, Levy S, Benes SC. Stem Cell Ophthalmology Treatment Study (SCOTS): bone marrow-derived stem cells in the treatment of Leber’s hereditary optic neuropathy. Neural Regen Res. 2016;11(10):1685-1694.
  • Weiss JN, Levy S, Benes SC. Stem Cell Ophthalmology Treatment Study: bone marrow derived stem cells in the treatment of non-arteritic ischemic optic neuropathy (NAION). Stem Cell Investig. 2017:23:94.
  • Weiss JN, Levy S. Stem Cell Ophthalmology Treatment Study: bone marrow derived stem cells in the treatment of Retinitis Pigmentosa. Stem Cell Investig. 2018;5:18.
  • Weiss JN, Levy S. Stem Cell Ophthalmology Treatment Study (SCOTS): bone marrow derived stem cells in the treatment of Usher syndrome. Stem Cell Investig. 2019;6:31.
  • Weiss JN, Levy S. Dynamic light scattering spectroscopy of the retina-a non-invasive quantitative technique to objectively document visual improvement following ocular stem cell treatment. Stem Cell Investig. 2019;6:8.
  • Kuriyan AE, Albini TA, Townsend JH, Rodriguez M, Pandya HK, Leonard RE, et al. Vision loss after intravitreal injection of autologous ‘stem cells’ for AMD. N Engl J Med 2017;376(11):1047–1053.
APA caglar c (2021). Stargardt ve Fundus Flavimaculatus; Güncel Tedavi ve Geliştirilmekte olanTedaviler. , 190 - 200.
Chicago caglar cagatay Stargardt ve Fundus Flavimaculatus; Güncel Tedavi ve Geliştirilmekte olanTedaviler. (2021): 190 - 200.
MLA caglar cagatay Stargardt ve Fundus Flavimaculatus; Güncel Tedavi ve Geliştirilmekte olanTedaviler. , 2021, ss.190 - 200.
AMA caglar c Stargardt ve Fundus Flavimaculatus; Güncel Tedavi ve Geliştirilmekte olanTedaviler. . 2021; 190 - 200.
Vancouver caglar c Stargardt ve Fundus Flavimaculatus; Güncel Tedavi ve Geliştirilmekte olanTedaviler. . 2021; 190 - 200.
IEEE caglar c "Stargardt ve Fundus Flavimaculatus; Güncel Tedavi ve Geliştirilmekte olanTedaviler." , ss.190 - 200, 2021.
ISNAD caglar, cagatay. "Stargardt ve Fundus Flavimaculatus; Güncel Tedavi ve Geliştirilmekte olanTedaviler". (2021), 190-200.
APA caglar c (2021). Stargardt ve Fundus Flavimaculatus; Güncel Tedavi ve Geliştirilmekte olanTedaviler. Güncel Retina Dergisi, 5(2), 190 - 200.
Chicago caglar cagatay Stargardt ve Fundus Flavimaculatus; Güncel Tedavi ve Geliştirilmekte olanTedaviler. Güncel Retina Dergisi 5, no.2 (2021): 190 - 200.
MLA caglar cagatay Stargardt ve Fundus Flavimaculatus; Güncel Tedavi ve Geliştirilmekte olanTedaviler. Güncel Retina Dergisi, vol.5, no.2, 2021, ss.190 - 200.
AMA caglar c Stargardt ve Fundus Flavimaculatus; Güncel Tedavi ve Geliştirilmekte olanTedaviler. Güncel Retina Dergisi. 2021; 5(2): 190 - 200.
Vancouver caglar c Stargardt ve Fundus Flavimaculatus; Güncel Tedavi ve Geliştirilmekte olanTedaviler. Güncel Retina Dergisi. 2021; 5(2): 190 - 200.
IEEE caglar c "Stargardt ve Fundus Flavimaculatus; Güncel Tedavi ve Geliştirilmekte olanTedaviler." Güncel Retina Dergisi, 5, ss.190 - 200, 2021.
ISNAD caglar, cagatay. "Stargardt ve Fundus Flavimaculatus; Güncel Tedavi ve Geliştirilmekte olanTedaviler". Güncel Retina Dergisi 5/2 (2021), 190-200.
Sayfa Oluşturulma Tarihi
23-04-2024 18:9

İLETİŞİM

TÜBİTAK ULAKBİM TR Dizin

Yüzüncüyıl, İşçi Blokları Mahallesi

Muhsin Yazıcıoğlu Caddesi No:51/C

06530 Çankaya / ANKARA +90 (312) 298 92 00

trdizin@tubitak.gov.tr

TÜBİTAK ULAKBİM Ulusal Akademik Ağ ve Bilgi Merkezi Cahit Arf Bilgi Merkezi © Tüm Hakları Saklıdır. Gizlilik Politikası Kullanım Şartları