Luigi Donato, Simona Alibrandi, Concetta Scimone, Rosalia D’Angelo, Antonina Sidoti
Abstract
Retinitis pigmentosa (RP) is a group of genetically heterogeneous diseases with mutations in more than 80 genes and different patterns of inheritance. Various factors make diagnosis of this blinding disease complex and lack of definitive cure increases the urgency to identify new drugs.
Animal models and innovative genome editing technologies are a powerful tools for the study of the molecular mechanisms leading to photoreceptor degeneration, feature of this disease.
Furthermore, they are the basis for therapeutic strategies aimed to retard or even stop disease progression.
In this review, the authors focus on animal models, describing their advantages and disadvantages, and CRISPR/Cas9 applications.
References
1. Na KH, Kim HJ, Kim KH, Han S, Kim P, Hann HJ, Ahn HS. Prevalence, Age at Diagnosis, Mortality, and Cause of Death in Retinitis Pigmentosa in Korea-A Nation wide Population-based Study. Am J Ophthalmol 2017;176:157-165.
2.NewmanA M, Gallo N B, Hancox LS, Miller NJ, RadekeCM, Maloney M A, Cooper JB, Hageman GS, Anderson DH, Johnson LV, Radeke MJ. Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks. Genome Medicine 2012;4:16.
3.Bravo-Gil N,González-del Pozo M, Martín-Sánchez M,Méndez-Vidal C, Rodríguez-de la Rúa E, Borrego S,Antiñolo G. Unravelling the genetic basis of simplex Retinitis Pigmentosa cases. Sci Rep 2017;7: 41937.
4. Niederriter AR, Davis EE, Golzio C, Oh EC, Tsai IC, Katsanis N. In Vivo Modeling of the Morbid Human Genome using Danio rerio. J Vis Exp 2013;78: 50338.
5. Zelinka CP, Sotolongo-Lopez M, Fadool JM.Targeted disruption of the endogenous zebrafish rhodopsin locus as models of rapid rod photoreceptor degeneration. Mol Vis 2018;24: 587–602
6. Garcia-Delgado AB, Valdés-Sánchez L, Calado SM, Diaz-Corrales FJ, Bhattacharya SS.Rasagiline delays retinal degeneration in a mouse model of retinitis pigmentosa via modulation of Bax/Bcl-2 expression. CNS Neurosci Ther 2018;245:448-455.
7. Gustavo D. Aguirre. Concepts and Strategies in Retinal Gene Therapy.Invest Ophthalmol Vis Sci 2017;58:5399–5411.
8. Chang GQ, Hao Y, Wong F. Apoptosis: final common pathway of photoreceptor death in rd, rds, and rhodopsin mutant mice. Neuron1993;11:595-605.
9. Steinberg RH, Flannery JG, Naash M. Transgenicrat models of inherited retinal degeneration caused by mutant opsin genes. Invest Ophthalmol Vis Sci 1996;37:S698.
10.Narfstrom K, Wrigstad A, Nilsson SE.The Briard dog: a new animal model of congenital stationary night blindness. Br J Ophthalmol1989;73:750-576.
11. Wrigstad A, Narfstrom K, Nilsson SE.Slowly progressive changes of the retina and retinal pigment epithelium in briard dogs with hereditary retinal dystrophy. A morphological study. Doc Ophthalmol 1994;87:337-354.
12. Koch S, Sothilingam V, Garcia Garrido M, Tanimoto N, Becirovic E, Koch F, Seide C, Beck S, Seeliger M, Biel M, Mühlfriedel R,Michalakis S. Gene therapy restores vision and delays degeneration in the CNGB1(-/-) mouse model of retinitis pigmentosa. HumMol Genet 2012;21: 4486-4496.
13. Tan MH, Smith AJ, Pawlyk B, Xu X, Liu X, Bainbridge J B,Basche M, McIntosh J, Tran HV, Nathwani A, Li T, Ali RR. Gene therapy for retinitis pigmentosa and Leber congenital amaurosis caused by defects in AIPL1: effective rescue of mouse models of partial and complete Aipl1 deficiency using AAV2/2 and AAV2/8 vectors. HumMol Genet 2009;18:2099-2114.
14. Petit L, Lhériteau E, Weber M, Le Meur G, Deschamps J, Provost N, Mendes-Madeira A, LibeauL, Guihal C, Colle M, Moullier P, Rolling F. Restoration of Vision in the pde6β-deficient Dog, a Large Animal Model of Rod-cone Dystrophy.Mol Ther 2012;20:2019-2030.
15. Fan N, Lai L. Genetically Modified Pig Models for Human Diseases. J Genet Genomics 2013;40:67-73.
16. Ganzen L, Venkatraman P, Pang CP, Leung YF, Zhang M. Utilizing Zebrafish Visual Behaviors in Drug Screening for Retinal Degeneration. Int J Mol Sci 2017;18. pii: E1185.
17. Richardson R,Tracey-White D, Webster A,Moosaje M. The zebrafish eye-a paradigm for investigating human ocular genetics. Eye (Lond) 2017;31:68-86.
18. Malicki J, Neuhauss S, Schier F, Solnica-Krezel L, Stemple L, Stainier Y R, Abdelilah S, Zwartkruis F, Rangini Z, Driever W. Mutations affecting development of the zebrafish retina. Cardiovascular Research Center 1996;123:263-273.
19. Fadool J, Dowling J. Zebrafish: A Model System for the Study of Eye Genetics. Progress in Retinal and Eye Research.ProgRetin Eye Res. 2008 ;27:89-110.
20. Nakao T, Tsujikawa M, Notomi S, Ikeda Y, Nishida K. The Role of Mislocalized Phototransduction in Photoreceptor Cell Death of Retinitis Pigmentosa. PLoS ONE 2012;7:e32472.
21. Stearns G, Evangelista M, Fadool JM, Brockerhoff SE. A Mutation in the Cone-Specific pde6 Gene Causes Rapid Cone Photoreceptor Degeneration in Zebrafish. J. Neurosci 2007;27:13866–13874.
22. Bakondi B, Lv W, Lu B, Jones MK, Tsai Y, Kim KJ, Levy R, Akhtar AA, Breunig JJ, Svendsen CN, Wang S. In vivo CRISPR/Cas9 gene editing correctsretinaldystrophy in the S334ter-3 rat model of autosomaldominantretinitis pigmentosa. MolTher 2016;24:556–563.
23.Shao M, Rui Xu T, Shi CHENC. The big bang of genome editing technology: development and application of the CRISPR/Cas9 system in disease animal models. 2016; 37: 191–204.
24. Arno G, Agrawal SA, Eblimit A,Bellingham J, Xu M, Wang F, Chakarova C, Parfitt DA, Lane A, Burgoyne T, Hull S, Carss KJ, Fiorentino A, Hayes MJ, Munro PM, Nicols R, Pontikos N, Holder GE,UKIRDC, Asomugha C, Raymond FL, Moore AT, Plagnol V, Michaelides M, Hardcastle AJ, Li Y, Cukras C, Webster AR, Cheetham ME, Chen R. Mutations in REEP6 cause autosomal-recessive retinitis pigmentosa. Am J Hum Genet 2016;99:1305–1315.
25. Wu WH, Tsai YT, Justus S, Lee TT, Zhang L, Lin CS, Bassuk AG, Mahajan VB, Tsang SH. CRISPR repair reveals causative mutation in a preclinical model of retinitis pigmentosa. Mol Ther 2016;24:1388–1394.
26. Latella MC, Di Salvo MT, Cocchiarella F, Benati D, Grisendi G, Comitato A, Marigo V, Recchia A. In vivo editing of the human mutant rhodopsin gene by electroporation of plasmid-based CRISPR/Cas9 in the mouse retina. Mol Ther Nucleic Acids 2016;5:e389.
