Cell technologies in retinitis pigmentosa treatment

Zeinet Akhmedyanova 1, Manshuk Yeltokova 2, Zhanna Bayanbayeva 1 * , Assel Khassenova 3
More Detail
1 Department of Eye Diseases, Astana Medical University, Astana, Kazakhstan
2 Department of Ophthalmology, National Scientific Medical Center, Astana, Kazakhstan
3 Department of Academic Quality Unit, School of Public Health, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
* Corresponding Author
J CLIN MED KAZ, Volume 19, Issue 2, pp. 4-8. https://doi.org/10.23950/jcmk/11931
OPEN ACCESS 476 Views 411 Downloads
Download Full Text (PDF)


The growing crucial problem in practical ophthalmology relates to growth of hereditary degenerative diseases of the retina, in particular retinitis, causing progressive loss of visual functions. According to international estimates, the incidence rate of hereditary dystrophy contains 1 case per 3000 population. With the development of biomedical cell technologies, transplantation of stem (autologous and allogeneic) cells is at the stage of active research.
The article reviewed literature sources on prevalence, risk factors, etiopathogenesis, diagnosis, clinical picture and treatment of retinitis pigmentosa.


Akhmedyanova Z, Yeltokova M, Bayanbayeva Z, Khassenova A. Cell technologies in retinitis pigmentosa treatment. J CLIN MED KAZ. 2022;19(2):4-8. https://doi.org/10.23950/jcmk/11931


  • Fay Newton and Roly Megaw. Mechanisms of Photoreceptor Death in Retinitis Pigmentosa. Genes (Basel). 2020; 11(10):1120. https://doi.org/10.3390/genes11101120
  • Wright A.F., Chakarova C.F., El-Aziz M.M.A., Bhattacharya S.S. Photoreceptor degeneration: Genetic and mechanistic dissection of a complex trait. Nat. Rev. Genet. 2010; 11:273–284. https://doi.org/10.1038 / nrg2717
  • Yeltokova M, Ulyanova O, Askarov M, Chernyshova A, Kozina L. Integral Hematologic Indices in the Evaluation of the Immunologic Reactivity of the Organism in a Patient With Complication of Type 1 Diabetes Mellitus: A Case of Diabetic Retinopathy After Autologous Mesenchymal Stem Cell Transplant. Exp Clin Transplant. 2019;17(1):234-235. https://doi.org/10.6002/ect.MESOT2018.P99
  • Megaw RD, Soares DC, Wright AF. RPGR: Its role in photoreceptor physiology, human disease, and future therapies. Exp Eye Res. 2015; 138:32-41. https://doi.org/10.1016/j.exer.2015.06.007
  • José-Alain Sahel , Katia Marazova Clinical characteristics and current therapies for inherited retinal degenerations. Cold Spring Harb Perspect Med. 2014; 16;5(2):a017111. https://doi.org/10.1101/cshperspect.a017111
  • Andrew Zheng, Yao Li and Stephen H Tsang. Personalized therapeutic strategies for patients with retinitis pigmentosa. Expert Opin Biol Ther. 2015; 15(3):391–402. https://doi.org/10.1517/14712598.2015.1006192
  • Prevalence of disabilities and associated health conditions among adults--United States, 2001. Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep. 2001; 50(7):120-5. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5007a3.htm
  • Vornholt K, Uitdewilligen S, Nijhuis FJ J. Factors affecting the acceptance of people with disabilities at work: a literature review. Occup Rehabil. 2013; 23(4):463-75. https://doi.org/10.1007/s10926-013-9426-0
  • Accessed on May 2013;Ret Net. The Retinal Information Network 2013. Retrieved from http://www.sph.uth.tmc.edu/RetNet
  • Accessed on May 2013; HGMD. Human Gene Mutation Database (Biobase Biological Databases) 2013. Retrieved from http://www.hgmd.cf.ac.uk
  • Fokkema IF, Taschner PE, Schaafsma GC, Celli J, Laros JF, den Dunnen JT. LOVD v.2.0: the next generation in gene variant databases. Hum Mutat. 2011; 32(5):557-63. https://doi.org/10.1002/humu.21438
  • Radi E, Formichi P, Battisti C, Federico A J. Apoptosis and oxidative stress in neurodegenerative diseases. J Alzheimers Dis. 2014; 42(3):125-52. https://doi.org/10.3233/JAD-132738
  • Choudhury S, Bhootada Y, Gorbatyuk O, Gorbatyuk M . Caspase-7 ablation modulates UPR, reprograms TRAF2-JNK apoptosis and protects T17M rhodopsin mice from severe retinal degeneration. Cell Death Dis. 2013; 4:e528. https://doi.org/10.1038/cddis.2013.34
  • Comitato A, Sanges D, Rossi A, Humphries MM, Marigo V. Activation of Bax in three models of retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2014; 55(6):3555-62. https://doi.org/10.1167/iovs.14-13917
  • Chen Y, Yang M, Wang ZJ. (Z)-7,4'-Dimethoxy-6-hydroxy-aurone-4-O-β-glucopyranoside mitigates retinal degeneration in Rd10 mouse model through inhibiting oxidative stress and inflammatory responses. Cutan Ocul Toxicol. 2020; 39(1):36-42. https://doi.org/10.1177/0960327120927439
  • Viringipurampeer IA, Gregory-Evans CY, Metcalfe AL, Bashar E, Moritz OL, Gregory-Evans K. Cell Death Pathways in Mutant Rhodopsin Rat Models Identifies Genotype-Specific Targets Controlling Retinal Degeneration. Mol Neurobiol. 2019; 56(3):1637-1652. https://doi.org/10.1007/s12035-018-1192-8
  • Vanden Berghe T, Linkermann A, Jouan-Lanhouet S, Walczak H, Vandenabeele P Nat. Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Rev Mol Cell Biol. 2014; 15(2):135-47. https://doi.org/10.1038/nrm3737
  • Ying Y, Padanilam BJ. Regulation of necrotic cell death: p53, PARP1 and cyclophilin D-overlapping pathways of regulated necrosis?. Cell Mol Life Sci. 2016; 73(11-12):2309-2324. https://doi.org/10.1007/s00018-016-2202-5
  • Dondelinger Y, Declercq W, Montessuit S, Roelandt R, Goncalves A, Bruggeman I, Hulpiau P, Weber K. Review MLKL compromises plasma membrane integrity by binding to phosphatidylinositol phosphates. Cell Rep. 2014; 22; 7(4):971-81. https://doi.org/10.1016/j.celrep.2014.04.026
  • Yang H, Fu Y, Liu X, Shahi PK, Mavlyutov TA, Li J, Yao A, Guo SZ, Pattnaik BR, Guo LW. Role of the sigma-1 receptor chaperone in rod and cone photoreceptor degenerations in a mouse model of retinitis pigmentosa. Mol Neurodegener. 2017; 12(1):68. https://doi.org/10.1186/s13024-017-0202-z
  • Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B 3rd, Stockwell BR. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012; 149(5):1060-72. https://doi.org/10.1016/j.cell.2012.03.042.
  • Fatokun AA, Dawson VL, Dawson TM Br J. Review Parthanatos: mitochondrial-linked mechanisms and therapeutic opportunities. Pharmacol. 2014; 171(8):2000-16. https://doi.org/10.1111/bph.12416
  • Yumnamcha T, Devi TS, Singh LP. Auranofin Mediates Mitochondrial Dysregulation and Inflammatory Cell Death in Human Retinal Pigment Epithelial Cells: Implications of Retinal Neurodegenerative Diseases. Front Neurosci. 2019; 13:1065. https://doi.org/10.3389/fnins.2019.01065.
  • Boya P, Esteban-Martínez L, Serrano-Puebla A, Gómez-Sintes R, Villarejo-Zori B. Review Autophagy in the eye: Development, degeneration, and aging. Prog Retin Eye Res. 2016; 55:206-245. https://doi.org/10.1016/j.preteyeres.2016.08.001
  • Rodríguez-Muela N, Hernández-Pinto AM, Serrano-Puebla A, García-Ledo L, Latorre SH, de la Rosa EJ, Boya P. Lysosomal membrane permeabilization and autophagy blockade contribute to photoreceptor cell death in a mouse model of retinitis pigmentosa. Cell Death Differ. 2015; 22(3):476-87. https://doi.org/10.1038/cdd.2014.203
  • Yao J, Qiu Y, Frontera E, Jia L, Khan NW, Klionsky DJ, Ferguson TA, Thompson DA, Zacks DN. Inhibiting autophagy reduces retinal degeneration caused by protein misfolding. Autophagy. 2018; 14(7):1226-1238. https://doi.org/10.1080/15548627.2018.1463121
  • Li Y, Wang C, Liu Y, You J, Su G. Autophagy, lysosome dysfunction and mTOR inhibition in MNU-induced photoreceptor cell damage. Tissue Cell. 2019; 61:98-108. https://doi.org/10.1016 / j.tice.2019.09.008
  • Tao Y, Cai L, Zhou D, Wang C, Ma Z, Dong X, Peng G. CoPP-Induced-Induced HO-1 Overexpression Alleviates Photoreceptor Degeneration With Rapid Dynamics: A Therapeutic Molecular Against Retinopathy. Invest Ophthalmol Vis Sci. 2019; 60(15):5080-5094. https://doi.org/10.1167/iovs.19-26876
  • Campochiaro PA, Strauss RW, Lu L, et al. Is There Excess Oxidative Stress and Damage in Eyes of Patients with Retinitis Pigmentosa?. Antioxid Redox Signal. 2015; 23(7):643-648. https://doi.org/10.1089/ars.2015.6327
  • Morizane Y, Morimoto N, Fujiwara A, Kawasaki R, Yamashita H, Ogura Y, Shiraga F. Incidence and causes of visual impairment in Japan: the first nation-wide complete enumeration survey of newly certified visually impaired individuals. Jpn J Ophthalmol. 2019; 63(1):26-33. https://doi.org/10.1007/s10384-018-0623-4
  • Murakami Y, Ishikawa K, Nakao S, Sonoda KH. Review Innate immune response in retinal homeostasis and inflammatory disorders. Prog Retin Eye Res. 2020; 74:100778. https://doi.org/10.1016/j.preteyeres.2019.100778
  • Ikeda Y, Nakatake S, Funatsu J, Fujiwara K, Tachibana T, Murakami Y, Hisatomi T, Yoshida S, Enaida H, Ishibashi T, Sonoda KH. Night-vision aid using see-through display for patients with retinitis pigmentosa. Japanese Journal of Ophthalmology. https://doi.org/10.1007/s10384-018-00644-5
  • Petit L, Ma S, Cipi J, Cheng SY, Zieger M, Hay N, Punzo C. Aerobic Glycolysis Is Essential for Normal Rod Function and Controls Secondary Cone Death in Retinitis Pigmentosa. Cell Rep. 2018; 23(9):2629-2642. https://doi.org/10.1016/j.celrep.2018.04.111
  • Campochiaro PA, Mir TA. Review The mechanism of cone cell death in Retinitis Pigmentosa. Prog Retin Eye Res. 2018; 62:24-37 https://doi.org/10.1016/j.preteyeres.2017.08.004
  • O’Sullivan J, Mullaney BG, Bhaskar SS, et al. A paradigm shift in the delivery of services for diagnosis of inherited retinal disease. J Med Genet. 2012; 49:322–326. https://doi.org/10.1136/jmedgenet-2012-100847
  • Littink KW, den Hollander AI, Cremers FP, Collin RW. The power of homozygosity mapping: discovery of new genetic defects in patients with retinal dystrophy. Adv Exp Med Biol. 2012; 723:345–351. https://doi.org/10.1007/978-1-4614-0631-0_45
  • SP Daiger, LS Sullivan, and SJ Bowne Genes and mutations causing retinitis pigmentosa Clin Genet. Author manuscript; available in PMC. 2014; 84(2): https://doi.org/10.1111/cge.12203
  • Shanks ME, Downes SM, Copley RR, et al. Next-generation sequencing (NGS) as a diagnostic tool for retinal degeneration reveals a much higher detection rate in early-onset disease. Eur J Hum Genet. 2013; 21:274–280. https://doi.org/10.1038/ejhg.2012.172
  • Elena B Domènech , Gemma Marfany The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies. Review. Antioxidants (Basel). 2020; 9(4):347. https://doi.org/10.3390/antiox9040347
  • Brennan TA, Wilson JM. The special case of gene therapy pricing. Nat Biotechnol. 2014; 32(9):874–6. https://doi.org/10.1038/nbt.3003
  • Vasireddy V, Mills JA, Gaddameedi R, et al. AAV-mediated gene therapy for choroideremia: preclinical studies in personalized models. PLoS One. 2013; 8(5):e61396. https://doi.org/10.1371/journal.pone.0061396
  • Adzhubei I, Jordan DM, Sunyaev SR. Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet. 2013;Chapter 7(Unit 7.20) https://doi.org/10.1002/0471142905.hg0720s76
  • Tucker BA, Mullins RF, Streb LM, et al. Patient-specific iPSC-derived photoreceptor precursor cells as a means to investigate retinitis pigmentosa. Elife. 2013; 2:e00824. https://doi.org/10.7554/eLife.00824
  • Yoshida T, Ozawa Y, Suzuki K, et al. The use of induced pluripotent stem cells to reveal pathogenic gene mutations and explore treatments for retinitis pigmentosa. Mol Brain. 2014; 7(1):45 https://doi.org/10.1186/1756-6606-7-45
  • Li Y, Wu W-H, Hsu C-W, et al. Gene therapy in patient-specific stem cell lines and a preclinical model of retinitis pigmentosa with membrane frizzled-related protein defects. Mol Ther. 2014; 22(9):1688–97. https://doi.org/10.1038/mt.2014.100
  • Busskamp V, Krol J, Nelidova D, Daum J, Szikra T, Tsuda B, Jüttner J, Farrow K, Scherf BG, Alvarez CP, Genoud C, Sothilingam V, Tanimoto N, Stadler M, Seeliger M, Stoffel M, Filipowicz W, Roska B. miRNAs 182 and 183 are necessary to maintain adult cone photoreceptor outer segments and visual function. Neuron 2014; 83(3):586-600. https://doi.org/10.1038/s41467-021-23627-6
  • Assawachananont J, Mandai M, Okamoto S, Yamada C, Eiraku M, Yonemura S, Sasai Y, Takahashi M. Transplantation of embryonic and induced pluripotent stem cell-derived 3D retinal sheets into retinal degenerative mice. Stem Cell Reports. 2014; 2(5):662-74. https://doi.org/10.1016/j.stemcr.2014.03.011
  • Tan H-K, Toh C-XD, Ma D, et al. Human finger-prick induced pluripotent stem cells facilitate the development of stem cell banking. Stem Cells Transl Med. 2014; 3(5):586–98. https://doi.org/10.5966/sctm.2013-0195
  • Wert KJ, Sancho-Pelluz J, Tsang SH. Mid-stage intervention achieves similar efficacy as conventional early-stage treatment using gene therapy in a pre-clinical model of retinitis pigmentosa. Hum Mol Genet. 2014; 23(2):514–23. https://doi.org/10.1093 / hmg /ddt452
  • Nakazawa M., Suzuki Y., Ito T., Metoki T., Kudo T., Ohguro H. Long-term effects of nilvadipine against progression of the central visual field defect in retinitis pigmentosa: an extended study. BioMed Research International. 2013; 2013:6. https://doi.org/10.1155/2013/585729.585729
  • Hoffman D. R., Hughbanks-Wheaton D. K., Pearson N. S., et al. Four-year placebo-controlled trial of docosahexaenoic acid in X-linked retinitis pigmentosa (DHAX Trial): a randomized clinical trial. JAMA Ophthalmology. 2014; 132(7):866–873. https://doi.org/10.1001/jamaophthalmol.2014.1634
  • Marta Sacchetti, 1 Flavio Mantelli Systematic Review of Randomized Clinical Trials on Safety and Efficacy of Pharmacological and Nonpharmacological Treatments for Retinitis Pigmentosa. J Ophthalmol. 2015; 737053. https://doi.org/10.1155/2015/737053