Diagnostics of inherited retinal degenerations by gene therapy

Close metadata

Recommended articles:

Polymorphism and modern diagnostic approaches for Leber congenital amaurosis. Russian Annals of Ophthalmology. 2024;(5):56-62

The article presents recent worldwide achievements in the area of diagnosis and treatment of inherited retinal degenerations (IRDs) from the standpoint of ophthalmic genetics. Clinical studies conducted in patients with Leber congenital amaurosis and retinitis pigmentosa caused by biallelic mutations in the RPE65 gene have provided the basis for future genes studies associated with IRDs. The conducted studies highlight the importance of fundamental understanding of function of the gene, timely diagnosis and study of natural history of the disease. Currently, surgical techniques are being improved for the efficient delivery of gene preparations to target cells, as well as the criteria for evaluating treatment outcomes.

Keywords:

Inherited retinal degenerations

Leber congenital amaurosis

retinitis pigmentosa

RPE65 gene

Authors:

Shurygina M.F.

S.N. Fedorov National Medical Research Center «MNTK «Eye Microsurgery»;
Center of Genetics and Reproductive Medicine «Genetico»

Khoteeva A.M.

S.N. Fedorov National Medical Research Center «MNTK «Eye Microsurgery»

Received:

09.06.2021

Accepted:

15.07.2021

List of references:

Pagon RA. Retinitis pigmentosa. Surv Ophthalmol. 1988;33(3):137-177. https://doi.org/10.1016/0039-6257(88)90085-9
Khlebnikova OV, Dadali EL Nasledstvennaya patologiya organa zreniya [Hereditary pathology of the organ of vision]. M.: Avtorskaya akademiya; 2014. (In Russ.).
Verbakel KS, van Huet RAC, Boon CJF. Non-syndromic retinitis pigmentosa. Prog Retin Eye Res. 2018;66:157-186. https://doi.org/10.1016/j.preteyeres.2018.03.005
Russell S, Bennett J, Wellman JA, Chung DC. 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. https://doi.org/10.1016/S0140-6736(17)31868-8
Heckenlively JR, Yoser SL, Friedman LH. Clinical Findings and Common Symptoms in Retinitis Pigmentosa. Am J Ophthalmol. 1988;105(5):504-511. https://doi.org/10.1016/0002-9394(88)90242-5
Strong S, Liew G, Michaelides M. Retinitis pigmentosa-associated cystoid macular oedema: pathogenesis and avenues of intervention. Br J Ophthalmol. 2017;101(1):31-37. https://doi.org/10.1136/bjophthalmol-2016-309376
Chebil A, Touati S, Maamouri R, et al. Spectral Domain optical coherence tomography findings in patients with retinitis pigmentosa. Tunis Med. 2016; 94(4):265-271.
Auffarth GU, Tetz MR, Krastel H, et al. [Complicated cataracts in various forms of retinitis pigmentosa. Type and incidence]. Ophthalmologe. 1997; 94(9):642-646. https://doi.org/10.1007/s003470050175
Yoshida N, Ikeda Y, Murakami Y, et al. Vitreous cysts in patients with retinitis pigmentosa. Jpn J Ophthalmol. 2015;59(6):373-377. https://doi.org/10.1007/s10384-015-0405-1
Grover S, Fishman GA, Brown JrJ. Frequency of optic disc or parapapillary nerve fiber layer drusen in retinitis pigmentosa. Ophthalmology. 1997;104: 295-298. https://doi.org/10.1016/s0161-6420(97)30321-2
Cehajic-Kapetanovic J, Xue K, de la Camara CM-F, Nanda A. Retinal gene therapy in X-linked retinitis pigmentosa caused by mutations in RPGR: Results at 6 months in a first in human clinical trial. Nat Med. 2020;26(3): 354-359. https://doi.org/10.1038/s41591-020-0763-1
Pinckers A, van Aarem A, Keunen JE. Colour vision in retinitis pigmentosa. Influence of cystoid macular edema. Int Ophthalmol. 1993;17:143-146.
Menghini M, Jolly JK, Nanda A, et al. Early cone photoreceptor outer segment length shortening in RPGR X-linked retinitis pigmentosa. Ophthalmologica. 2020. https://doi.org/10.1159/000507484
Sujirakul T, Davis R, Erol D, et al. Bilateral Concordance of the Fundus Hyperautofluorescent Ring in Typical Retinitis Pigmentosa Patients. Ophthalmic Genet. 2015;36(2):113-122. https://doi.org/10.3109/13816810.2013.841962
Novak-Lauš K, Kukulj S, Zorić-Geber M, Bastaić O. Primary tapetoretinal dystrophies as the cause of blindness and impaired vision in the republic of Croatia. Acta Clinica Croatica. 2002;41(1):23-27.
Hamel C. Retinitis pigmentosa. Orphanet J Rare Dis. 2006;1:40. https://doi.org/10.1186/1750-1172-1-40
Kumaran N, Moore AT, Weleber RG, Michaelides M. Leber congenital maurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions. Br J Ophthalmol. 2017;101(9):1147-1154. https://doi.org/10.1136/bjophthalmol-2016-309975
Stone EM. Leber congenital amaurosis — a model for efficient genetic testing of heterogeneous disorders: LXIV Edward Jackson Memorial Lecture. Am J Ophthalmol. 2007;144:791-811. https://doi.org/10.1016/j.ajo.2007.08.022
Den Hollander AI, Roepman R, Koenekoop RK, Cremers FP. Leber congenital amaurosis: genes, proteins and disease mechanisms. Prog Retin Eye Res. 2008;27(4):391-419.
Shamshinova AM, ed. Nasledstvennye i vrozhdennye zabolevaniya setchatki i zritel’nogo nerva [Hereditary and congenital diseases of the retina and optic nerve]. M.: Meditsina; 2001. (In Russ.).
Sonksen PM, Dale N. Visual impairment in infancy: impact on neurodevelopmental and neurobiological processes. Dev Med Child Neurol. 2002;44: 782-791. https://doi.org/10.1017/s0012162201002936
Zahid S, Branham K, Schlegel D, et al. Retinal Dystrophy Gene Atlas. Springer. 2018;280. https://doi.org/10.1007/978-3-319-10867-4
Maguire AM, Simonelli F, Pierce EA, et al. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med. 2008;358:2240-2248.
Peddle CF, Fry LE, McClements ME, MacLaren RE. CRISPR Interference-Potential Application in Retinal Disease. Int J Mol Sci. 2020;21(7):2329. https://doi.org/10.3390/ijms21072329
Morimura H, Fishman GA, Grover SA, Fulton AB, et al. Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis. Proc Natl Acad Sci USA. 1998;95:3088-3093.
Thompson DA, Gyurus P, Fleischer LL, et al. Genetics and phenotypes of RPE65 mutations in inherited retinal degeneration. Invest Ophthalmol Vis Sci. 2000;41:4293-4299.
U.S. National Library of medicine. Clinicaltrials.gov. https://clinicaltrials.gov/
Chung DC, Bertelsen M, Lorenz B, et al. The natural history of inherited retinal dystrophy due to biallelic mutations in the RPE65 Gene. Am J Ophthalmol. 2019;199:58-70. https://doi.org/10.1016/j.ajo.2018.09.024
Langelaan M, Wouters B, Moll AC, et al. Functional Field Score: The Effect of Using a Goldmann V-4e Isopter Instead of a Goldmann III-4e Isopter. Invest Ophthalmol Vis Sci. 2006;47:1817-1823. https://doi.org/10.1167/iovs.04-1345
Katz ML, Redmond TM. Effect of Rpe65 knockout on accumulation of lipofuscin fluorophores in the retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2001;42(12):3023-3030.
Katz ML, Wendt KD, Sanders DN. RPE65 gene mutation prevents development of autofluorescence in retinal pigment epithelial phagosomes Mech Ageing Dev. 2005;126(4):513-521. https://doi.org/10.1016/j.mad.2004.11.004.
Bainbridge JWB, Smith AJ, Barker SS, et al. Effect of gene therapy on visual function in Leber’s congenital amaurosis. N Engl J Med. 2008;358(21): 2231-2239. https://doi.org/10.1056/NEJMoa0802268
Hauswirth WW, Aleman TS, Kaushal S, et al. 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):979-990. https://doi.org/10.1089/hum.2008.107
Burnight ER, Gupta M, Wiley LA, et al. Using CRISPR-Cas9 to Generate Gene-Corrected Autologous iPSCs for the Treatment of Inherited Retinal Degeneration. Mol Ther. 2017;25(9):1999-2013. https://doi.org/10.1016/j.ymthe.2017.05.015
Ledford H. CRISPR treatment inserted directly into the body for first time. Nature. 2020;579(7798):185. https://doi.org/10.1038/d41586-020-00655-8
Clérin E, Marussig M, Sahel J-A, Léveillard T. Metabolic and Redox Signaling of the Nucleoredoxin-Like-1 Gene for the Treatment of Genetic Retinal Diseases. Int J Mol Sci. 2020;21(5):1625. https://doi.org/10.3390/ijms21051625
Garita-Hernandez M, Lampič M, Chaffiol A, et al. Restoration of visual function by transplantation of optogenetically engineered photoreceptors. Nat Commun. 2019;10(1):4524. https://doi.org/10.1038/s41467-019-12330-2
Davis JL, Gregori NZ, MacLaren RE, Lam BL. Surgical Technique for Subretinal Gene Therapy in Humans with Inherited Retinal Degeneration. Retina. 2019;39(suppl 1):2-8. https://doi.org/10.1097/IAE.0000000000002609.
Hussain RM, Tran KD, Maguire AM, Berrocal AM. Subretinal Injection of Voretigene Neparvovec-rzyl in a Patient With RPE65-Associated Leber’s Congenital Amaurosis. Ophthalmic Surg Lasers Imaging Retina. 2019;50(10): 661-663. https://doi.org/10.3928/23258160-20191009-01
Feuer WJ, Schiffman JC, Davis JL, et al. Gene therapy for leber hereditary optic neuropathy: initial results. Ophthalmology. 2016;123:558-570. https://doi.org/10.1016/j.ophtha.2015.10.025
Fan KC, Yannuzzi NA, Patel NA, et al. Surgical Techniques for the Subretinal Delivery of Pediatric Gene Therapy. Ophthalmol Retina. 2020;4(6): 644-645. https://doi.org/10.1016/j.oret.2020.01.023

Close metadata