Research status of ciliary dysfunction and visual development related diseases_Chinese Journal of Ocular Fundus Diseases

Authors：

Feng Yuelan ¹ ,  Li Ningdong ²

1. Department of Ophthalmology, The First Affiliated Hospital of Baotou Medical College, Baotou 014010, China;
2. Department of Ophthalmology, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China;

Corresponding?author：

Li Ningdong, Email: lnd30@163.com

Keywords：

Photoreceptor connecting cilium; Retinitis pigmentosa; Leber congenital amaurosis; Usher syndromes; Review

DOI：

10.3760/cma.j.cn511434-20190213-00044

Video：

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Abstract Full text Figures/Tables Video References Cited by

Cilia are hair-like protuberance on cells of the human body that play a vital role in organs generation and maintenance. Abnormalities of ciliary structure and function affect almost every system of the body, such as the brain, eyes, liver, kidney, bone, reproductive system and so on. Retinal photoreceptor cells are one of sensory neurons which convert light stimuli into neurological responses. This process, called phototransduction, takes place in the outer segments (OS) of rod and cone photoreceptors. OS are specialized sensory cilia, and disruptions in cilia genes, which are causative in a growing number of non-syndromic retinal dystrophies, such as retinitis pigmentosa, Leber’s congenital amaurosis. These syndromes are genetically heterogeneous, involving mutations in a large number of genes. They show considerable clinical and genetic overlap. At present, there are few researches on retinal ciliopathies and clinical treatment strategy. This review shows a comprehensive overview of ciliary dysfunction and visual development related diseases, which contributes to understand the characteristics of these diseases and take early intervention in clinic.

Citation： Feng Yuelan, Li Ningdong. Research status of ciliary dysfunction and visual development related diseases. Chinese Journal of Ocular Fundus Diseases, 2020, 36(8): 652-656. doi: 10.3760/cma.j.cn511434-20190213-00044 Copy

1.	Joachimiak E, W?oga D, Filipek A, et al. Ciliopaties-diseases caused by abnormal cilia functioning[J]. Postepy Biochem, 2018, 64(4): 338-350. DOI: 10.18388/pb.2018_148.
2.	Reiter JF, Leroux MR. Genes and molecular pathways underpinning ciliopathies[J]. Nat Rev Mol Cell Biol, 2017, 18(9): 533-547. DOI: 10.1038/nrm.2017.60.
3.	Lee JE, Gleeson JG. Cilia in the nervous system: linking cilia function and neurodevelopmental disorders[J]. Curr Opin Neurol, 2011, 24(2): 98-105. DOI: 10.1097/WCO.0b013e3283444d05.
4.	Rao Damerla R, Gabriel GC, Li Y, et al. Role of cilia in structural birth defects: insights from ciliopathy mutant mouse models[J]. Birth Defects Res C Embryo Today, 2014, 102(2): 115-125. DOI: 10.1002/bdrc.21067.
5.	Bujakowska KM, Liu Q, Pierce EA. Photoreceptor cilia and retinal ciliopathies[J/OL]. Cold Spring Harb Perspect Biol, 2017, 9(10): a028274[2017-10-03]. http://europepmc.org/article/MED/28289063. DOI: 10.1101/cshperspect.a028274.
6.	Ramamurthy V, Cayouette M. Development and disease of the photoreceptor cilium[J]. Clin Genet, 2009, 76(2): 137-145. DOI: 10.1111/j.1399-0004.2009.01240.x.
7.	Khanna H. Photoreceptor sensory cilium: traversing the ciliary gate[J]. Cells, 2015, 4(4): 674-686. DOI: 10.3390/cells4040674.
8.	Wheway G, Parry DA, Johnson CA. The role of primary cilia in the development and disease of the retina[J]. Organogenesis, 2014, 10(1): 69-85. DOI: 10.4161/org.26710.
9.	Estrada-Cuzcano A, Roepman R, Cremers F, et al. Non-syndromic retinal ciliopathies: translating gene discovery into therapy[J]. Hum Mol Genet, 2012, 21(R1): R111-R124. DOI: 10.1093/hmg/dds298.
10.	He Y, Zhang Y, Su G, et al. Recent advances in treatment of retinitis pigmentosa[J]. Curr Stem Cell Res Ther, 2015, 10(3): 258-265. DOI: 10.2174/1574888x09666141027103552.
11.	Takkar B, Bansal P, Venkatesh P. Leber's congenital cmaurosis and gene therapy[J]. Indian J Pediatr, 2018, 85(3): 237-242. DOI: 10.1007/s12098-017-2394-1.
12.	Sheck L, Davies W, Moradi P, et al. Leber congenital amaurosis associated with mutations in CEP290, clinical phenotype, and natural history in preparation for trials of novel therapies[J]. Ophthalmology, 2018, 125(6): 894-903. DOI: 10.1016/j.ophtha.2017.12.013.
13.	Tsang SH, Sharma T, et al. Progressive cone dystrophy and cone-rod dystrophy (XL, AD, and AR)[J]. Adv Exp Med Biol, 2018, 1085: 53-60. DOI: 10.1007/978-3-319-95046-4_12.
14.	Braun DA, Hildebrandt Fl. Ciliopathies[J/OL]. Cold Spring Harb Perspect Biol, 2017, 9(3): a028191[2017-03-01]. http://europepmc.org/article/MED/27793968. DOI: 10.1101/cshperspect.a028191.
15.	Zhang Q, Yu D, Seo S, et al. Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential assembly of stable bardet-biedl syndrome protein complex, the BBSome[J]. J Biol Chem, 2012, 287(24): 20625-20635. DOI: 10.1074/jbc.M112.341487.
16.	Castro-Sánchez S, álvarez-Satta M, Valverde D. Bardet-Biedl syndrome: a rare genetic disease[J]. J Pediatr Genet, 2013, 2(2): 77-83. DOI: 10.3233/PGE-13051.
17.	Denniston AK, Beales PL, Tomlins PJ, et al. Evaluation of visual function and needs in adult patients with bardet-biedl syndrome[J]. Retina, 2014, 34(11): 2282-2289. DOI: 10.1097/IAE.0000000000000222.
18.	Bonnet C, El-Amraoui A. Usher syndrome (sensorineural deafness and retinitis pigmentosa): pathogenesis, molecular diagnosis and therapeutic approaches[J]. Curr Opin Neurol, 2012, 25(1): 42-49. DOI: 10.1097/WCO.0b013e32834ef8b2.
19.	Mathur P, Yang J. Usher syndrome: hearing loss, retinal degeneration and associated abnormalities[J]. Biochim Biophys Acta, 2015, 1852(3): 406-420. DOI: 10.1016/j.bbadis.2014.11.020.
20.	álvarez-Satta M, Castro-Sánchez S, Valverde D. Alstr?m syndrome: current perspectives[J]. Appl Clin Genet, 2015, 8: 171-179. DOI: 10.2147/TACG.S56612.
21.	Collin GB, Marshall JD, King BL, et al. The Alstrom syndrome protein, ALMS1, interacts with alpha-actinin and components of the endosome recycling pathway[J/OL]. PLoS One, 2012, 7(5): e37925[2012-05-31]. http://europepmc.org/article/MED/22693585. DOI: 10.1371/journal.pone.0037925.
22.	Manara R, Citton V, Maffei P, et al. Degeneration and plasticity of the optic pathway in Alstr?m syndrome[J]. AJNR Am J Neuroradiol, 2015, 36(1): 160-165. DOI: 10.3174/ajnr.A4115.
23.	Lu Q, Insinna C, Ott C, et al. Early steps in primary ciliumassembly require EHD1/EHD3-dependent ciliary vesicle formation[J]. Nat Cell Biol, 2015, 17(3): 228-240. DOI: 10.1038/ncb3109.
24.	Xu W, Jin M, Hu R, et al. The Joubert syndrome protein Inpp5e controls ciliogenesis by regulating phosphoinositides at the apical membrane[J]. J Am Soc Nephrol, 2017, 28(1): 118-129. DOI: 10.1681/ASN.2015080906.
25.	Valente EM, Dallapiccola B, Bertini E. Joubert syndrome and related disorders[J]. Handb Clin Neurol, 2013, 113: 1879-1888. DOI: 10.1016/B978-0-444-59565-2.00058-7.
26.	Szymanska K, Hartill V, Johnson CA. Unraveling the genetics of Joubert and Meckel-Gruber syndromes[J]. J Pediatr Genet, 2015, 3(2): 65-78. DOI: 10.3233/PGE-14090.
27.	Zhang R, Chen S, Han P, et al. Whole exome sequencing identified a homozygous novel variant in CEP290 gene causes Meckel syndrome[J]. J Cell Mol Med, 2020, 24(2): 1906-1916. DOI: 10.1111/jcmm.14887.
28.	Ronquillo CC, Bernstein PS, Baehr W. Senior-Loken syndrome: a syndromic form of retinal dystrophy associated with nephronophthisis[J]. Vis Res, 2012, 75: 88-97. DOI: 10.1016/j.visres.
29.	Hemachandar R. Senior-loken syndrome-a ciliopathy[J/OL]. J Clin Diagn Res, 2014, 8(11): MD04-5[2014-11-20]. http://europepmc.org/article/MED/25584255. DOI: 10.7860/JCDR/2014/9688.5120.

1. Joachimiak E, W?oga D, Filipek A, et al. Ciliopaties-diseases caused by abnormal cilia functioning[J]. Postepy Biochem, 2018, 64(4): 338-350. DOI: 10.18388/pb.2018_148.
2. Reiter JF, Leroux MR. Genes and molecular pathways underpinning ciliopathies[J]. Nat Rev Mol Cell Biol, 2017, 18(9): 533-547. DOI: 10.1038/nrm.2017.60.
3. Lee JE, Gleeson JG. Cilia in the nervous system: linking cilia function and neurodevelopmental disorders[J]. Curr Opin Neurol, 2011, 24(2): 98-105. DOI: 10.1097/WCO.0b013e3283444d05.
4. Rao Damerla R, Gabriel GC, Li Y, et al. Role of cilia in structural birth defects: insights from ciliopathy mutant mouse models[J]. Birth Defects Res C Embryo Today, 2014, 102(2): 115-125. DOI: 10.1002/bdrc.21067.
5. Bujakowska KM, Liu Q, Pierce EA. Photoreceptor cilia and retinal ciliopathies[J/OL]. Cold Spring Harb Perspect Biol, 2017, 9(10): a028274[2017-10-03]. http://europepmc.org/article/MED/28289063. DOI: 10.1101/cshperspect.a028274.
6. Ramamurthy V, Cayouette M. Development and disease of the photoreceptor cilium[J]. Clin Genet, 2009, 76(2): 137-145. DOI: 10.1111/j.1399-0004.2009.01240.x.
7. Khanna H. Photoreceptor sensory cilium: traversing the ciliary gate[J]. Cells, 2015, 4(4): 674-686. DOI: 10.3390/cells4040674.
8. Wheway G, Parry DA, Johnson CA. The role of primary cilia in the development and disease of the retina[J]. Organogenesis, 2014, 10(1): 69-85. DOI: 10.4161/org.26710.
9. Estrada-Cuzcano A, Roepman R, Cremers F, et al. Non-syndromic retinal ciliopathies: translating gene discovery into therapy[J]. Hum Mol Genet, 2012, 21(R1): R111-R124. DOI: 10.1093/hmg/dds298.
10. He Y, Zhang Y, Su G, et al. Recent advances in treatment of retinitis pigmentosa[J]. Curr Stem Cell Res Ther, 2015, 10(3): 258-265. DOI: 10.2174/1574888x09666141027103552.
11. Takkar B, Bansal P, Venkatesh P. Leber's congenital cmaurosis and gene therapy[J]. Indian J Pediatr, 2018, 85(3): 237-242. DOI: 10.1007/s12098-017-2394-1.
12. Sheck L, Davies W, Moradi P, et al. Leber congenital amaurosis associated with mutations in CEP290, clinical phenotype, and natural history in preparation for trials of novel therapies[J]. Ophthalmology, 2018, 125(6): 894-903. DOI: 10.1016/j.ophtha.2017.12.013.
13. Tsang SH, Sharma T, et al. Progressive cone dystrophy and cone-rod dystrophy (XL, AD, and AR)[J]. Adv Exp Med Biol, 2018, 1085: 53-60. DOI: 10.1007/978-3-319-95046-4_12.
14. Braun DA, Hildebrandt Fl. Ciliopathies[J/OL]. Cold Spring Harb Perspect Biol, 2017, 9(3): a028191[2017-03-01]. http://europepmc.org/article/MED/27793968. DOI: 10.1101/cshperspect.a028191.
15. Zhang Q, Yu D, Seo S, et al. Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential assembly of stable bardet-biedl syndrome protein complex, the BBSome[J]. J Biol Chem, 2012, 287(24): 20625-20635. DOI: 10.1074/jbc.M112.341487.
16. Castro-Sánchez S, álvarez-Satta M, Valverde D. Bardet-Biedl syndrome: a rare genetic disease[J]. J Pediatr Genet, 2013, 2(2): 77-83. DOI: 10.3233/PGE-13051.
17. Denniston AK, Beales PL, Tomlins PJ, et al. Evaluation of visual function and needs in adult patients with bardet-biedl syndrome[J]. Retina, 2014, 34(11): 2282-2289. DOI: 10.1097/IAE.0000000000000222.
18. Bonnet C, El-Amraoui A. Usher syndrome (sensorineural deafness and retinitis pigmentosa): pathogenesis, molecular diagnosis and therapeutic approaches[J]. Curr Opin Neurol, 2012, 25(1): 42-49. DOI: 10.1097/WCO.0b013e32834ef8b2.
19. Mathur P, Yang J. Usher syndrome: hearing loss, retinal degeneration and associated abnormalities[J]. Biochim Biophys Acta, 2015, 1852(3): 406-420. DOI: 10.1016/j.bbadis.2014.11.020.
20. álvarez-Satta M, Castro-Sánchez S, Valverde D. Alstr?m syndrome: current perspectives[J]. Appl Clin Genet, 2015, 8: 171-179. DOI: 10.2147/TACG.S56612.
21. Collin GB, Marshall JD, King BL, et al. The Alstrom syndrome protein, ALMS1, interacts with alpha-actinin and components of the endosome recycling pathway[J/OL]. PLoS One, 2012, 7(5): e37925[2012-05-31]. http://europepmc.org/article/MED/22693585. DOI: 10.1371/journal.pone.0037925.
22. Manara R, Citton V, Maffei P, et al. Degeneration and plasticity of the optic pathway in Alstr?m syndrome[J]. AJNR Am J Neuroradiol, 2015, 36(1): 160-165. DOI: 10.3174/ajnr.A4115.
23. Lu Q, Insinna C, Ott C, et al. Early steps in primary ciliumassembly require EHD1/EHD3-dependent ciliary vesicle formation[J]. Nat Cell Biol, 2015, 17(3): 228-240. DOI: 10.1038/ncb3109.
24. Xu W, Jin M, Hu R, et al. The Joubert syndrome protein Inpp5e controls ciliogenesis by regulating phosphoinositides at the apical membrane[J]. J Am Soc Nephrol, 2017, 28(1): 118-129. DOI: 10.1681/ASN.2015080906.
25. Valente EM, Dallapiccola B, Bertini E. Joubert syndrome and related disorders[J]. Handb Clin Neurol, 2013, 113: 1879-1888. DOI: 10.1016/B978-0-444-59565-2.00058-7.
26. Szymanska K, Hartill V, Johnson CA. Unraveling the genetics of Joubert and Meckel-Gruber syndromes[J]. J Pediatr Genet, 2015, 3(2): 65-78. DOI: 10.3233/PGE-14090.
27. Zhang R, Chen S, Han P, et al. Whole exome sequencing identified a homozygous novel variant in CEP290 gene causes Meckel syndrome[J]. J Cell Mol Med, 2020, 24(2): 1906-1916. DOI: 10.1111/jcmm.14887.
28. Ronquillo CC, Bernstein PS, Baehr W. Senior-Loken syndrome: a syndromic form of retinal dystrophy associated with nephronophthisis[J]. Vis Res, 2012, 75: 88-97. DOI: 10.1016/j.visres.
29. Hemachandar R. Senior-loken syndrome-a ciliopathy[J/OL]. J Clin Diagn Res, 2014, 8(11): MD04-5[2014-11-20]. http://europepmc.org/article/MED/25584255. DOI: 10.7860/JCDR/2014/9688.5120.

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