Current research status of retinal ciliopathy

2026，No. 07, Current Issue, Highlights, Review
Comments

Authors: Fan Xue, Rong Weining

Corresponding author: Rong Weining, Email: moc.621624gniniewgnor

Published:2026-07-10

DOI: 10.3760/cma.j.cn115989-20230731-00054

Download PDF
Read Full Text

ABSTRACT 

Cilia widely exist in most cell types of the human body, and the dysfunction of cilia can affect various organs. The outer segment of the photoreceptor is a kind of highly differentiated primary sensory cilium, and its structure and function are damaged after gene mutation, which causes the obstruction of material transport between the inner and outer segment of the photoreceptor, and then leads to the degeneration of the photoreceptor and retina. Retinal ciliopathy can be divided into two categories according to its phenotype: non-syndromic retinal ciliopathy and syndromic retinal ciliopathy. Syndromic retinal ciliopathy is associated with abnormalities in other organs in addition to ocular manifestations. Common retinal ciliopathies include retinitis pigmentosa, Leber congenital amaurosis, Bardet-Biedl syndrome, Usher syndrome, etc. At present, the main treatments of retinal ciliopathies are symptomatic treatment and gene therapy, but this can only benefit a small number of patients, and a large number of studies are needed to support the treatment of retinal ciliopathies. Based on the current research status of ciliopathy at home and abroad, this paper summarizes the genotypes and clinical phenotypes of retinal ciliopathy, aiming to provide a certain theoretical framework for further research on ciliopathy and subsequent gene therapy.

KEYWORDS：

Retina;Ciliopathy;Gene;Clinical phenotype;Genotype

COPYRIGHTS:

Copyright by Chinese Medical Association

No content published by the journals of Chinese Medical Association may be reproduced or abridged without authorization. Please do not use or copy the layout and design of the journals without permission.

All articles published represent the opinions of the authors, and do not reflect the official policy of the Chinese Medical Association or the Editorial Board, unless this is clearly specified.

Authors Info & Affiliations 

Fan Xue

Third Clinical Medical College of Ningxia Medical University, Ningxia Eye Hospital, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, China

Rong Weining

Third Clinical Medical College of Ningxia Medical University, Ningxia Eye Hospital, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, China

📚 Citation formats

GB/T 7714 format

APA 7th format

References(click to collapse)
  • [1]Sánchez-Bellver L ,Toulis V ,Marfany G . On the wrong track: alterations of ciliary transport in inherited retinal dystrophies[J]. Front Cell Dev Biol, 2021,9∶623734. DOI: 10.3389/fcell.2021.623734 .
  • [2]Wright AF ,Chakarova CF ,AbdEl-Aziz MM ,et al. Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait[J]. Nat Rev Genet, 2010,11(4)∶273-284. DOI: 10.1038/nrg2717 .
  • [3]Estrada-Cuzcano A ,Roepman R ,Cremers FP ,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 .
  • [4]Bujakowska KM ,Liu Q ,Pierce EA . Photoreceptor cilia and retinal ciliopathies[J]. Cold Spring Harb Perspect Biol, 2017,9(10)∶a028274. DOI: 10.1101/cshperspect.a028274 .
  • [5]Stone EM ,Andorf JL ,Whitmore SS ,et al. Clinically focused molecular investigation of 1000 consecutive families with inherited retinal disease[J]. Ophthalmology, 2017,124(9)∶1314-1331. DOI: 10.1016/j.ophtha.2017.04.008 .
  • [6]Chen HY ,Kelley RA ,Li T ,et al. Primary cilia biogenesis and associated retinal ciliopathies[J]. Semin Cell Dev Biol, 2021,110∶70-88. DOI: 10.1016/j.semcdb.2020.07.013 .
  • [7]Guo D ,Ru J ,Xie L ,et al. Tmem138 is localized to the connecting cilium essential for rh odopsin localization and outer segment biogenesis [J/OL]. Proc Natl Acad Sci U S A, 2022,119(15)∶e2109934119[2025-10-20]. https://pubmed.ncbi.nlm.nih.gov/35394880/. DOI: 10.1073/pnas.2109934119 .
  • [8]Hazim RA ,Fisher SK ,Williams DS . The photoreceptor outer segment: development and renewal[J]. Curr Top Dev Biol, 2025,165∶493-528. DOI: 10.1016/bs.ctdb.2025.07.002 .
  • [9]Nakayama K ,Katoh Y . Architecture of the IFT ciliary trafficking machinery and interplay between its components[J]. Crit Rev Biochem Mol Biol, 2020,55(2)∶179-196. DOI: 10.1080/10409238.2020.1768206 .
  • [10]Pigino G . Intraflagellar transport[J]. Curr Biol, 2021,31(10)∶R530-R536. DOI: 10.1016/j.cub.2021.03.081 .
  • [11]Chen HY ,Welby E ,Li T ,et al. Retinal disease in ciliopathies: recent advances with a focus on stem cell-based therapies[J]. Transl Sci Rare Dis, 2019,4(1-2)∶97-115. DOI: 10.3233/TRD-190038 .
  • [12]Taub DG ,Liu Q . The role of intraflagellar transport in the photoreceptor sensory cilium[J]. Adv Exp Med Biol, 2016,854∶627-633. DOI: 10.1007/978-3-319-17121-083 .
  • [13]Sharon D ,Banin E . Nonsyndromic retinitis pigmentosa is highly prevalent in the Jerusalem region with a high frequency of founder mutations[J]. Mol Vis, 2015,21∶783-792.
  • [14]Mansergh FC ,Millington-Ward S ,Kennan A ,et al. Retinitis pigmentosa and progressive sensorineural hearing loss caused by a C12258A mutation in the mitochondrial MTTS2 gene[J]. Am J Hum Genet, 1999,64(4)∶971-985. DOI: 10.1086/302344 .
  • [15]Lestienne P ,Ponsot G . Kearns-Sayre syndrome with muscle mitochondrial DNA deletion[J]. Lancet, 1988,1(8590)∶885. DOI: 10.1016/s0140-6736(88)91632-7 .
  • [16]Hu YS ,Song H ,Li Y ,et al. Whole-exome sequencing identifies novel mutations in genes responsible for retinitis pigmentosa in 2 nonconsanguineous Chinese families[J]. Int J Ophthalmol, 2019,12(6)∶915-923. DOI: 10.18240/ijo.2019.06.06 .
  • [17]deBruijn SE ,Verbakel SK ,deVrieze E ,et al. Homozygous variants in KIAA1549 , encoding a ciliary protein, are associated with autosomal recessive retinitis pigmentosa [J]. J Med Genet, 2018,55(10)∶705-712. DOI: 10.1136/jmedgenet-2018-105364 .
  • [18]Beheshtian M ,SaeeRad S ,Babanejad M ,et al. Impact of whole exome sequencing among Iranian patients with autosomal recessive retinitis pigmentosa[J]. Arch Iran Med, 2015,18(11)∶776-785.
  • [19]Perrault I ,Saunier S ,Hanein S ,et al. Mainzer-Saldino syndrome is a ciliopathy caused by IFT140 mutations [J]. Am J Hum Genet, 2012,90(5)∶864-870. DOI: 10.1016/j.ajhg.2012.03.006 .
  • [20]Chakarova CF ,Papaioannou MG ,Khanna H ,et al. Mutations in TOPORS cause autosomal dominant retinitis pigmentosa with perivascular retinal pigment epithelium atrophy [J]. Am J Hum Genet, 2007,81(5)∶1098-1103. DOI: 10.1086/521953 .
  • [21]He K ,Zhou Y ,Li N . Mutations of TOPORS identified in families with retinitis pigmentosa [J]. Ophthalmic Genet, 2022,43(3)∶371-377. DOI: 10.1080/13816810.2022.2039721 .
  • [22]Ran J ,Zhou J . Targeting the photoreceptor cilium for the treatment of retinal diseases[J]. Acta Pharmacol Sin, 2020,41(11)∶1410-1415. DOI: 10.1038/s41401-020-0486-3 .
  • [23]Riera M ,Abad-Morales V ,Navarro R ,et al. Expanding the retinal phenotype of RP1: from retinitis pigmentosa to a novel and singular macular dystrophy[J]. Br J Ophthalmol, 2020,104(2)∶173-181. DOI: 10.1136/bjophthalmol-2018-313672 .
  • [24]Goldberg AF ,Moritz OL ,Williams DS . Molecular basis for photoreceptor outer segment architecture[J]. Prog Retin Eye Res, 2016,55∶52-81. DOI: 10.1016/j.preteyeres.2016.05.003 .
  • [25]Chiu W ,Lin TY ,Chang YC ,et al. An update on gene therapy for inherited retinal dystrophy: experience in Leber congenital amaurosis clinical trials[J]. Int J Mol Sci, 2021,22(9)∶4534. DOI: 10.3390/ijms22094534 .
  • [26]冯月兰，李宁东. 纤毛功能障碍与视觉发育相关疾病的关系研究现状[J]. 中华眼底病杂志， 2020,36(8)∶652-656. DOI: 10.3760/cma.j.cn511434-20190213-00044 .
  • Feng YL , Li ND . Research status of ciliary dysfunction and visual development related diseases[J]. Chin J Ocul Fundus Dis, 2020,36(8)∶652-656. DOI: 10.3760/cma.j.cn511434-20190213-00044 .
  • [27]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 .
  • [28]Wu Z ,Pang N ,Zhang Y ,et al. CEP290 is essential for the initiation of ciliary transition zone assembly[J/OL]. PLoS Biol, 2020,18(12)∶e3001034[2025-10-20]. https://pubmed.ncbi.nlm.nih.gov/33370260/. DOI: 10.1371/journal.pbio.3001034 .
  • [29]Tsang SH ,Sharma T . 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 .
  • [30]Sharif AS ,Yu D ,Loertscher S ,et al. C8ORF37 is required for photoreceptor outer segment disc morphogenesis by maintaining outer segment membrane protein homeostasis[J]. J Neurosci, 2018,38(13)∶3160-3176. DOI: 10.1523/JNEUROSCI.2964-17.2018 .
  • [31]Luoma-Overstreet G ,Jewell A ,Brar V ,et al. Occult macular dystrophy: a case report and major review[J]. Ophthalmic Genet, 2022,43(5)∶703-708. DOI: 10.1080/13816810.2022.2089361 .
  • [32]Ayyagari R ,Demirci FY ,Liu J ,et al. X-linked recess ive atrophic macular degeneration from RPGR mutation [J]. Genomics, 2002,80(2)∶166-171. DOI: 10.1006/geno.2002.6815 .
  • [33]Noel N ,MacDonald IM . RP1L1 and inherited photoreceptor disease: a review[J]. Surv Ophthalmol, 2020,65(6)∶725-739. DOI: 10.1016/j.survophthal.2020.04.005 .
  • [34]Patnaik SR ,Zhang X ,Biswas L ,et al. RPGR protein complex regulates proteasome activity and mediates store-operated calcium entry[J]. Oncotarget, 2018,9(33)∶23183-23197. DOI: 10.18632/oncotarget.25259 .
  • [35]Nadal J ,Iglesias M . Long-term visual outcomes and rehabilitation in Usher syndrome type Ⅱ after retinal implant Argus Ⅱ[J]. BMC Ophthalmol, 2018,18(1)∶205. DOI: 10.1186/s12886-018-0880-5 .
  • [36]Gill JS ,Georgiou M ，Kalitzeos A ,et al. Progressive cone and cone-rod dystrophies: clinical features, molecular genetics and prospects for therapy[J]. Br J Ophthalmol. 2019,103(5)∶711-720. DOI: 10.1136/bjophthalmol-2018-313278 .
  • [37]彭海鹰，周钟强，史平玲，等. Leber先天性黑朦一家系 CRB1 基因新突变 [J]. 中华实验眼科杂志， 2020,38(9)∶780-782. DOI: 10.3760/cma.j.cn115989-20190813-00347 .
  • Peng HY , Zhou ZQ , Shi PL ,et al. Novel mutation in the CRB1 gene in a family affected withLeber congenital amaurosis [J]. Chin J Exp Ophthalmol, 2020,38(9)∶780-782. DOI: 10.3760/cma.j.cn115989-20190813-00347 .
  • [38]Fortnum HM ,Summerfield AQ ,Marshall DH ,et al. Prevalence of permanent childhood hearing impairment in the United Kingdom and implications for universal neonatal hearing screening: questionnaire based ascertainment study [J]. BMJ, 2001,323(7312)∶536-540. DOI: 10.1136/bmj.323.7312.536 .
  • [39]Fuster-García C ,García-Bohórquez B ,Rodríguez-Muñoz A ,et al. Usher syndrome: genetics of a human ciliopathy[J]. Int J Mol Sci, 2021,22(13)∶6723. DOI: 10.3390/ijms22136723 .
  • [40]Khateb S ,Kowalewski B ,Bedoni N ,et al. A homozygous founder missense variant in arylsulfatase G abolishes its enzymatic activity causing atypical Usher syndrome in humans[J]. Genet Med, 2018,20(9)∶1004-1012. DOI: 10.1038/gim.2017.227 .
  • [41]Méndez-Vidal C ,González-DelPozo M ,Vela-Boza A ,et al. Whole-exome sequencing identifies novel compound heterozygous mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosa [J]. Mol Vis, 2013,19∶2187-2195.
  • [42]Liu X ,Bulgakov KN ,Darrow B ,et al. Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells[J]. Proc Natl Acad Sci USA, 2007,104(11)∶4413-4418. DOI: 10.1073/pnas.0610950104 .
  • [43]Alhamoud M ,Alnosair G ,Alhashim H . Bardet-Biedl syndrome: a rare case from ophthalmology perspective[J/OL]. Cureus, 2022,14(10)∶e29912[2025-10-26]. https://pubmed.ncbi.nlm.nih.gov/36348931/. DOI: 10.7759/cureus.29912 .
  • [44]Nachury MV ,Loktev AV ,Zhang Q ,et al. A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis[J]. Cell, 2007,129(6)∶1201-1213. DOI: 10.1016/j.cell.2007.03.053 .
  • [45]Masek M ,Etard C ,Hofmann C ,et al. Loss of the Bardet-Biedl protein Bbs1 alters photoreceptor outer segment protein and lipid composition[J]. Nat Commun, 2022,13(1)∶1282. DOI: 10.1038/s41467-022-28982-6 .
  • [46]Choudhury AR ,Munonye I ,Sanu KP ,et al. A review of Alström syndrome: a rare monogenic ciliopathy[J]. Intractable Rare Dis Res, 2021,10(4)∶257-262. DOI: 10.5582/irdr.2021.01113 .
  • [47]Hearn T . ALMS1 and Alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits[J]. J Mol Med (Berl), 2019,97(1)∶1-17. DOI: 10.1007/s00109-018-1714-x .
  • [48]Álvarez-Satta M ,Lago-Docampo M ,Bea-Mascato B ,et al. ALMS1 regulates TGF-β signaling and morphology of primary cilia[J]. Front Cell Dev Biol, 2021,9∶623829. DOI: 10.3389/fcell.2021.623829 .
  • [49]Tsang SH ,Aycinena A ,Sharma T . Ciliopathy: Alström syndrome[J]. Adv Exp Med Biol, 2018,1085∶179-180. DOI: 10.1007/978-3-319-95046-4_35 .
  • [50]Qi Y ,Lu J ,Sun N ,et al. Alström syndrome: a rare cause of dilated cardiomyopathy in five Chinese children[J]. Gene, 2025,944∶149285. DOI: 10.1016/j.gene.2025.149285 .
  • [51]Álvarez-Satta M ,Castro-Sánchez S ,Valverde D . Alström syndrome: current perspectives[J]. Appl Clin Genet, 2015,8∶171-179. DOI: 10.2147/TACG.S56612 .
  • [52]Shi X ,Garcia G ,VanDeWeghe JC ,et al. Super-r esolution microscopy reveals that disruption of ciliary transition-zone architecture causes Joubert syndrome [J]. Nat Cell Biol, 2017,19(10)∶1178-1188. DOI: 10.1038/ncb3599 .
  • [53]Maria BL ,Hoang KB ,Tusa RJ ,et al. ” Joubert syndrome ” revisited: key ocular motor signs with magnetic resonance imaging correlation [J]. J Child Neurol, 1997,12(7)∶423-430. DOI: 10.1177/088307389701200703 .
  • [54]Brancati F ,Dallapiccola B ,Valente EM . Joubert syndrome and related disorders[J]. Orphanet J Rare Dis, 2010,5∶20. DOI: 10.1186/1750-1172-5-20 .
  • [55]Casteleyn T ,Vogt M ,Weichert A ,et al. Prenatal diagnosis of joubert syndrome 23 with left isomerism: a novel phenotype associated with pathogenic KIAA0586 variant[J]. Prenat Diagn, 2025,45(13)∶1783-1786. DOI: 10.1002/pd.70008 .
  • [56]Sangermano R ,Deitch I ,Peter VG ,et al. Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD [J]. NPJ Genom Med, 2021,6(1)∶53. DOI: 10.1038/s41525-021-00214-8 .
  • [57]Leightner AC ,Hommerding CJ ,Peng Y ,et al. The Meckel syndrome protein meckelin ( TMEM67 ) is a key regulator of cilia function but is not required for tissue planar polarity [J]. Hum Mol Genet, 2013,22(10)∶2024-2040. DOI: 10.1093/hmg/ddt054 .
  • [58]Khurana S ,Saini V ,Wadhwa V ,et al. Meckel-Gruber syndrome: ultrasonographic and fetal autopsy correlation[J]. J Ultrasound, 2017,20(2)∶167-170. DOI: 10.1007/s40477-016-0231-4 .
  • [59]Hartill V ,Szymanska K ,Sharif SM ,et al. Meckel-Gruber syndrome: an update on diagnosis, clinical management, and research advances[J]. Front Pediatr, 2017,5∶244. DOI: 10.3389/fped.2017.00244 .
  • [60]Tsang SH ,Aycinena A ,Sharma T . Ciliopathy: senior-Løken syndrome[J]. Adv Exp Med Biol, 2018,1085∶175-178. DOI: 10.1007/978-3-319-95046-4_34 .
  • [61]崔洁媛，张宏文. 肾单位肾痨及其相关纤毛病研究进展[J]. 中国生育健康杂志， 2017,28(2)∶195-197，封3. DOI: 10.3969/j.issn.1671-878X.2017.02.029 .
  • [62]Adams NA ,Awadein A ,Toma HS . The retinal ciliopathies[J]. Ophthalmic Genet, 2007,28(3)∶113-125. DOI: 10.1080/13816810701537424 .
  • [63]Hildebrandt F ,Otto E . Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease？[J]. Nat Rev Genet, 2005,6(12)∶928-940. DOI: 10.1038/nrg1727 .
  • [64]Bruel AL ,Franco B ,Duffourd Y ,et al. Fifteen years of research on oral-facial-digital syndromes: from 1 to 16 causal genes[J]. J Med Genet, 2017,54(6)∶371-380. DOI: 10.1136/jmedgenet-2016-104436 .
  • [65]Franco B ,Thauvin-Robinet C . Update on oral-facial-digital syndromes (OFDS)[J]. Cilia, 2016,5∶12. DOI: 10.1186/s13630-016-0034-4 .
  • [66]Athanasiou D ,Afanasyeva T ,Chai N ,et al. Small molecule treatment alleviates photoreceptor cilia defects in LCA5-deficient human retinal organoids[J]. Acta Neuropathol Commun, 2025,13(1)∶26. DOI: 10.1186/s40478-025-01943-y .
  • [67]Wheway G ,Lord J ,Baralle D . Splicing in the pathogenesis, diagnosis and treatment of ciliopathies[J]. Biochim Biophys Actaq Gene Regul Mech, 2019,1862(11-12)∶194433. DOI: 10.1016/j.bbagrm.2019.194433 .
  • [68]Datta P ,Ruffcorn A ,Seo S . Limited time window for retinal gene therapy in a preclinical model of ciliopathy[J]. Hum Mol Genet, 2020,29(14)∶2337-2352. DOI: 10.1093/hmg/ddaa124 .

 

(Read 3 times, 3 visits today)