Visual system pathology in a canine model of CLN5 neuronal ceroid lipofuscinosis.
Alleles
Animals
Autophagy
Disease Models, Animal
Dog Diseases
/ genetics
Dogs
Electroretinography
/ veterinary
Evoked Potentials, Visual
/ physiology
Female
Homozygote
Lysosomal Membrane Proteins
/ genetics
Male
Neuronal Ceroid-Lipofuscinoses
/ genetics
Phagocytosis
Retina
/ physiopathology
Retinal Degeneration
/ genetics
Vision, Ocular
Autophagy
Dog
Lysosomal storage
Phagocytosis
Photoreceptor cells
Retinal degeneration
Retinal pigment epithelium
Journal
Experimental eye research
ISSN: 1096-0007
Titre abrégé: Exp Eye Res
Pays: England
ID NLM: 0370707
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
20
05
2021
revised:
17
06
2021
accepted:
28
06
2021
pubmed:
4
7
2021
medline:
9
10
2021
entrez:
3
7
2021
Statut:
ppublish
Résumé
CLN5 neuronal ceroid lipofuscinosis is a hereditary neurodegenerative disease characterized by progressive neurological decline, vision loss and seizures. Visual impairment in children with CLN5 disease is attributed to a progressive decline in retinal function accompanied by retinal degeneration as well as impaired central nervous system function associated with global brain atrophy. We studied visual system pathology in five Golden Retriever littermates homozygous for the CLN5 disease allele previously identified in the breed. The dogs exhibited signs of pronounced visual impairment by 21-22 months of age. Electroretinogram recordings showed a progressive decline in retinal function primarily affecting cone neural pathways. Altered visual evoked potential recordings indicated that disease progression affected visual signal processing in the brain. Aside from several small retinal detachment lesions, no gross retinal abnormalities were observed with in vivo ocular imaging and histologically the retinas did not exhibit apparent abnormalities by 23 months of age. However, there was extensive accumulation of autofluorescent membrane-bound lysosomal storage bodies in almost all retinal layers, as well as in the occipital cortex, by 20 months of age. In the retina, storage was particularly pronounced in retinal ganglion cells, the retinal pigment epithelium and in photoreceptor cells just interior to the outer limiting membrane. The visual system pathology of CLN5-affected Golden Retrievers is similar to that seen early in the human disease. It was not possible to follow the dogs to an advanced stage of disease progression due to the severity of behavioral and motor disease signs by 23 months of age. The findings reported here indicate that canine CLN5 disease will be a useful model of visual system disease in CLN5 neuronal ceroid lipofuscinosis. The baseline data obtained in this investigation will be useful in future therapeutic intervention studies. The findings indicate that there is a fairly broad time frame after disease onset within which treatments could be effective in preserving vision.
Identifiants
pubmed: 34216614
pii: S0014-4835(21)00252-9
doi: 10.1016/j.exer.2021.108686
pmc: PMC8429270
mid: NIHMS1723638
pii:
doi:
Substances chimiques
Lysosomal Membrane Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108686Subventions
Organisme : NEI NIH HHS
ID : R01 EY031674
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
Références
Invest Ophthalmol Vis Sci. 2013 Aug 13;54(8):5432-40
pubmed: 23847311
Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2686-95
pubmed: 18344450
J Neurosci. 2016 Aug 3;36(31):8238-49
pubmed: 27488642
Neurobiol Dis. 2014 Feb;62:543-50
pubmed: 24269732
Exp Cell Res. 2017 Aug 1;357(1):40-50
pubmed: 28442266
Exp Eye Res. 2009 Nov;89(5):618-28
pubmed: 19523943
Genomics. 2005 Sep;86(3):287-94
pubmed: 16033706
Hum Mutat. 2009 May;30(5):E651-61
pubmed: 19309691
Hum Mutat. 2010 Mar;31(3):356-65
pubmed: 20052765
Exp Eye Res. 2021 Jun;207:108600
pubmed: 33930398
Sci Rep. 2017 May 9;7(1):1597
pubmed: 28487519
J Neuropathol Exp Neurol. 1997 Apr;56(4):369-75
pubmed: 9100667
Mech Ageing Dev. 1989 Jul;49(1):23-40
pubmed: 2747298
Brain. 2015 Apr;138(Pt 4):862-74
pubmed: 25724202
Brain Behav. 2015 Oct 09;5(11):e00401
pubmed: 26664787
Exp Eye Res. 2016 Nov;152:77-87
pubmed: 27637672
Neurology. 2010 Feb 16;74(7):565-71
pubmed: 20157158
Ann Ophthalmol. 1974 Dec;6(12):1299-1307
pubmed: 4440978
Acta Neuropathol Commun. 2018 Dec 27;6(1):145
pubmed: 30591081
Mol Ther. 2018 Oct 3;26(10):2366-2378
pubmed: 30078766
Nat Genet. 1998 Jul;19(3):286-8
pubmed: 9662406
Neuropediatrics. 1991 May;22(2):92-6
pubmed: 1649978
Invest Ophthalmol Vis Sci. 2001 Nov;42(12):3023-30
pubmed: 11687551
Exp Eye Res. 2016 May;146:276-282
pubmed: 27039708
Neurology. 2005 Feb 22;64(4):740-2
pubmed: 15728307
Doc Ophthalmol. 2013 Oct;127(2):79-87
pubmed: 23728902
Neurobiol Dis. 2017 Apr;100:62-74
pubmed: 28065762
J Am Vet Med Assoc. 1990 Aug 1;197(3):361-4
pubmed: 2391273
J Vet Intern Med. 2016 Jul;30(4):1149-58
pubmed: 27203721
Hum Mol Genet. 2002 Apr 15;11(8):885-91
pubmed: 11971870
Biochim Biophys Acta Mol Basis Dis. 2020 Sep 1;1866(9):165571
pubmed: 31678159
N Engl J Med. 2018 May 17;378(20):1898-1907
pubmed: 29688815
PLoS One. 2013 Sep 10;8(9):e74299
pubmed: 24058541
Cell Mol Life Sci. 2021 May;78(10):4735-4763
pubmed: 33792748
Hum Mol Genet. 2015 Dec 15;24(24):7060-74
pubmed: 26450516
Neurology. 2000 Aug 22;55(4):579-81
pubmed: 10953198
J Vet Med Sci. 2005 Sep;67(9):869-75
pubmed: 16210797
Biochim Biophys Acta. 2006 Oct;1762(10):890-7
pubmed: 16935476
Mol Genet Metab. 2015 Jun-Jul;115(2-3):101-9
pubmed: 25934231
Brain Behav. 2018 Sep;8(9):e01096
pubmed: 30136763
Mol Cell Biol. 2012 May;32(10):1855-66
pubmed: 22431521
J Vet Med Sci. 2006 Jan;68(1):79-82
pubmed: 16462123
Exp Eye Res. 2014 Aug;125:164-72
pubmed: 24954537
Invest Ophthalmol Vis Sci. 2018 Oct 1;59(12):5082-5097
pubmed: 30372735
Exp Eye Res. 2020 Mar;192:107926
pubmed: 31931002
Mol Genet Metab. 2019 May;127(1):107-115
pubmed: 31101435
Mech Ageing Dev. 2005 Apr;126(4):513-21
pubmed: 15722110
Vision Res. 1990;30(9):1291-303
pubmed: 2219746
Doc Ophthalmol. 2004 Mar;108(2):107-14
pubmed: 15455793
Exp Eye Res. 2020 Sep;198:108135
pubmed: 32634395
J Child Neurol. 2018 Nov;33(13):837-850
pubmed: 30264640
Exp Eye Res. 2020 Aug;197:108130
pubmed: 32622066
Pediatr Neurol. 1992 Mar-Apr;8(2):121-6
pubmed: 1580955
Hum Mutat. 2013 Dec;34(12):1688-97
pubmed: 24038957
Neurobiol Dis. 2008 Feb;29(2):306-15
pubmed: 17988881
Mol Genet Metab. 2006 Nov;89(3):245-53
pubmed: 16814585
Eur J Paediatr Neurol. 2001;5 Suppl A:157-61
pubmed: 11588989
J Neurosci Res. 2014 Nov;92(11):1591-8
pubmed: 24938720
Doc Ophthalmol. 2005 Jul;111(1):39-48
pubmed: 16502306
J Vet Intern Med. 1990 Jul-Aug;4(4):222-5
pubmed: 2401969
Dev Med Child Neurol. 2017 Aug;59(8):815-821
pubmed: 28542837
J Neurosci Res. 2014 Apr;92(4):531-41
pubmed: 24375814
Exp Eye Res. 2015 May;134:123-32
pubmed: 25697710
Exp Eye Res. 1986 Oct;43(4):561-73
pubmed: 3792460
Ophthalmology. 2000 Sep;107(9):1746-53
pubmed: 10964839
Exp Eye Res. 1984 Feb;38(2):137-51
pubmed: 6714331
Sci Transl Med. 2015 Nov 11;7(313):313ra180
pubmed: 26560358
Aust Vet J. 1991 Apr;68(4):137-40
pubmed: 2069541
Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1663-72
pubmed: 12657607
Curr Eye Res. 2018 Aug;43(8):1019-1023
pubmed: 29641909
Exp Cell Res. 2015 Oct 15;338(1):45-53
pubmed: 26342652
Neuropediatrics. 1982 Aug;13(3):135-41
pubmed: 7133332