Top

Published in:

Open Access 01-12-2019 | Pigmentary Retinopathy | Research

Comparison of structural progression between ciliopathy and non-ciliopathy associated with autosomal recessive retinitis pigmentosa

Authors: Vitor K. L. Takahashi, Christine L. Xu, Júlia T. Takiuti, Mary Ben L. Apatoff, Jimmy K. Duong, Vinit B. Mahajan, Stephen H. Tsang

Published in: Orphanet Journal of Rare Diseases | Issue 1/2019

Abstract

Background

To evaluate and compare the progression of ciliopathy and non-ciliopathy autosomal recessive Retinitis Pigmentosa patients (arRP) by measuring the constriction of hyperautofluorescent rings in fundus autofluorescence (FAF) images and the progressive shortening of the ellipsoid zone line width obtained by spectral-domain optical coherence tomography (SD-OCT).

Results

For the ciliopathy group, the estimated mean shortening of the ellipsoid zone line was 259 μm per year and the ring area decreased at a rate of 2.46 mm² per year. For the non-ciliopathy group, the estimated mean shortening of the ellipsoid zone line was 84 μm per year and the ring area decreased at a rate of 0.7 mm² per year.

Conclusions

Our study was able to quantify and compare the loss of EZ line width and short-wavelength autofluorescence (SW-AF) ring constriction progression over time for ciliopathy and non-ciliopathy arRP genes. These results may serve as a basis for modeling RP disease progression, and furthermore, they could potentially be used as endpoints in clinical trials seeking to promote cone and rod survival in RP patients.

Boughman JA, Conneally PM, Nance WE. Population genetic studies of retinitis pigmentosa. Am J Hum Genet. 1980;32(2):223–35 http://www.ncbi.nlm.nih.gov/pubmed/7386458.PubMedPubMedCentral

Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006;368(9549):1795–809. https://doi.org/10.1016/S0140-6736(06)69740-7.PubMedCrossRef

Estrada-Cuzcano A, Roepman R, Cremers FPM, Den HA, Mans DA. Non-syndromic retinal ciliopathies: Translating gene discovery into therapy. Hum Mol Genet. 2012;21(R1). https://doi.org/10.1093/hmg/dds298.PubMedCrossRef

Adams NA, Awadein A, Toma HS. The retinal ciliopathies. Ophthalmic Genet. 2007;28(3):113–25. https://doi.org/10.1080/13816810701537424.PubMedCrossRef

Patnaik SR, Raghupathy RK, Zhang X, Mansfield D, Shu X. The role of RPGR and its interacting proteins in ciliopathies. J Ophthalmol. 2015;2015. https://doi.org/10.1155/2015/414781.CrossRef

Hunter DG, Fishman GA, Kretzer FL. Abnormal axonemes in X-linked retinitis pigmentosa. Arch Ophthalmol. 1988. https://doi.org/10.1001/archopht.1988.01060130388028.PubMedCrossRef

Hunter DG, Mehta RS, Kretzer FL, Fishman GA. Abnormal sperm and photoreceptor Axonemes in Usher’s syndrome. Arch Ophthalmol. 1986. https://doi.org/10.1001/archopht.1986.01050150085033.PubMedCrossRef

Yang J, Liu X, Zhao Y, et al. Ablation of whirlin long isoform disrupts the USH2 protein complex and causes vision and hearing loss. PLoS Genet. 2010. https://doi.org/10.1371/journal.pgen.1000955.PubMedPubMedCentralCrossRef

Peters KR, Palade GE, Schneider BG, Papermaster DS. Fine structure of a periciliary ridge complex of frog retinal rod cells revealed by ultrahigh resolution scanning electron microscopy. J Cell Biol. 1983. https://doi.org/10.1083/jcb.96.1.265.PubMedCrossRef

10.

Mykytyn K, Sheffield VC. Establishing a connection between cilia and Bardet-Biedl syndrome. Trends Mol Med. 2004. https://doi.org/10.1016/j.molmed.2004.01.003.PubMedCrossRef

11.

Pazour GJ, Baker SA, Deane JA, et al. The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance. J Cell Biol. 2002. https://doi.org/10.1083/jcb.200107108.PubMedPubMedCentralCrossRef

12.

Wolfrum U, Schmitt A. Rhodopsin transport in the membrane of the connecting cilium of mammalian photoreceptor cells. Cell Motil Cytoskeleton. 2000. https://doi.org/10.1002/1097-0169(200006)46:2<95::AID-CM2>3.0.CO;2-Q.

13.

Apatoff MBL, Sengillo JD, White EC, et al. Autologous stem cell therapy for inherited and acquired retinal disease. Regen Med. 2018;13(1):89–96. https://doi.org/10.2217/rme-2017-0089.PubMedPubMedCentralCrossRef

14.

Smith J, Ward D, Michaelides M, Moore AT, Simpson S. New and emerging technologies for the treatment of inherited retinal diseases: a horizon scanning review. Eye. 2015. https://doi.org/10.1038/eye.2015.115.PubMedPubMedCentralCrossRef

15.

Lima LH, Cella W, Greenstein VC, et al. Structural assessment of hyperautofluorescent ring in patients with retinitis pigmentosa. Retina. 2009;29(7):1025–31. https://doi.org/10.1097/IAE.0b013e3181ac2418.PubMedPubMedCentralCrossRef

16.

Robson AG, Saihan Z, Jenkins SA, et al. Functional characterisation and serial imaging of abnormal fundus autofluorescence in patients with retinitis pigmentosa and normal visual acuity. Br J Ophthalmol. 2006. https://doi.org/10.1136/bjo.2005.082487.PubMedCrossRef

17.

Robson AG, Lenassi E, Saihan Z, et al. Comparison of fundus autofluorescence with Photopic and scotopic fine matrix mapping in patients with retinitis Pigmentosa: 4- to 8-year follow-up. Investig Opthalmology Vis Sci. 2012;53(10):6187. https://doi.org/10.1167/iovs.12-10195.CrossRef

18.

Sujirakul T, Davis R, Erol D, et al. Bilateral concordance of the fundus Hyperautofluorescent ring in typical retinitis Pigmentosa patients. Ophthalmic Genet. 2015. https://doi.org/10.3109/13816810.2013.841962.PubMedPubMedCentralCrossRef

19.

Nigg EA, Raff JW. Centrioles, centrosomes, and cilia in health and disease. Cell. 2009. https://doi.org/10.1016/j.cell.2009.10.036.PubMedCrossRef

20.

Novarino G, Akizu N, Gleeson JG. Modeling human disease in humans: the ciliopathies. Cell. 2011. https://doi.org/10.1016/j.cell.2011.09.014.PubMedPubMedCentralCrossRef

21.

Lima LH, Burke T, Greenstein VC, et al. Progressive constriction of the hyperautofluorescent ring in retinitis pigmentosa. Am J Ophthalmol. 2012;153(4):718–27.e2. https://doi.org/10.1016/j.ajo.2011.08.043.PubMedCrossRef

22.

Sujirakul T, Lin MK, Duong J, Wei Y, Lopez-Pintado S, Tsang SH. Multimodal imaging of central retinal disease progression in a 2-year mean follow-up of retinitis Pigmentosa. Am J Ophthalmol. 2015;160(4):786–798e4. https://doi.org/10.1016/j.ajo.2015.06.032.PubMedPubMedCentralCrossRef

23.

Cabral T, Sengillo JD, Duong JK, et al. Retrospective analysis of structural disease progression in retinitis Pigmentosa utilizing multimodal imaging. Sci Rep. 2017;7(1):10347. https://doi.org/10.1038/s41598-017-10473-0.PubMedPubMedCentralCrossRef

24.

Hamel C. Retinitis pigmentosa. Orphanet J Rare Dis. 2006;1:40. https://doi.org/10.1186/1750-1172-1-40.PubMedPubMedCentralCrossRef

25.

Meindl A, Dry K, Herrmann K, et al. A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3). Nat Genet. 1996. https://doi.org/10.1038/ng0596-35.PubMedCrossRef

26.

Vervoort R, Lennon A, Bird AC, et al. Mutational hot spot within a new RPGR exon in X-linked retinitis pigmentosa. Nat Genet. 2000. https://doi.org/10.1038/78182.PubMedCrossRef

27.

Iannaccone B, Wang K, Normando F, Baldi H, Macdonald CB, Baldi F, Cosgrove D, Morton CC, Swaroop A, Jablonski MM. Clinical and immunohistochemical evidence for an X linked retinitis pigmentosa syndrome with recurrent infections and hearing loss in association with an RPGR mutation. J Med Genet. 2003. https://doi.org/10.1136/jmg.40.11.e118.CrossRef

28.

Cai CX, Locke KG, Ramachandran R, Birch DG, Hood DC. A comparison of progressive loss of the ellipsoid zone (EZ) band in autosomal dominant and X-linked retinitis pigmentosa. Investig Ophthalmol Vis Sci. 2014;55(11):7417–22. https://doi.org/10.1167/iovs.14-15013.CrossRef

29.

Han Z, Conley SM, Naash MI. AAV and compacted DNA nanoparticles for the treatment of retinal disorders: challenges and future prospects. Investig Ophthalmol Vis Sci. 2011;52(6):3051–9. https://doi.org/10.1167/iovs.10-6916.CrossRef

30.

Seyedahmadi BJ, Rivolta C, Keene JA, Berson EL, Dryja TP. Comprehensive screening of the USH2A gene in usher syndrome type II and non-syndromic recessive retinitis pigmentosa. Exp Eye Res. 2004. https://doi.org/10.1016/j.exer.2004.03.005.PubMedCrossRef

Title: Comparison of structural progression between ciliopathy and non-ciliopathy associated with autosomal recessive retinitis pigmentosa
Authors: Vitor K. L. Takahashi
Christine L. Xu
Júlia T. Takiuti
Mary Ben L. Apatoff
Jimmy K. Duong
Vinit B. Mahajan
Stephen H. Tsang
Publication date: 01-12-2019
Publisher: BioMed Central
Keyword: Pigmentary Retinopathy
Published in: Orphanet Journal of Rare Diseases / Issue 1/2019
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-019-1163-9

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Comparison of structural progression between ciliopathy and non-ciliopathy associated with autosomal recessive retinitis pigmentosa

Abstract

Background

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2019

Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes

Clinical and genetic spectrum of sarcoglycanopathies in a large cohort of Chinese patients

SMArtCARE - A platform to collect real-life outcome data of patients with spinal muscular atrophy

Angioedema due to acquired C1-inhibitor deficiency: spectrum and treatment with C1-inhibitor concentrate

Epidemiological and clinical characteristics of symptomatic hereditary transthyretin amyloid polyneuropathy: a global case series

Update on the management of colchicine resistant Familial Mediterranean Fever (FMF)