Vision Loss in Juvenile Neuronal Ceroid Lipofuscinosis (CLN3 Disease)

Overview

Journal Ann N Y Acad Sci

Specialty Science

Date 2016 Jan 11

PMID 26748992

Citations 18

Authors

Madhu M Ouseph

Mark E Kleinman

Qing Jun Wang

Affiliations

Soon will be listed here.

Abstract

Juvenile neuronal ceroid lipofuscinosis (JNCL; also known as CLN3 disease) is a devastating neurodegenerative lysosomal storage disorder and the most common form of Batten disease. Progressive visual and neurological symptoms lead to mortality in patients by the third decade. Although ceroid-lipofuscinosis, neuronal 3 (CLN3) has been identified as the sole disease gene, the biochemical and cellular bases of JNCL and the functions of CLN3 are yet to be fully understood. As severe ocular pathologies manifest early in disease progression, the retina is an ideal tissue to study in the efforts to unravel disease etiology and design therapeutics. There are significant discrepancies in the ocular phenotypes between human JNCL and existing murine models, impeding investigations on the sequence of events occurring during the progression of vision impairment. This review focuses on current understanding of vision loss in JNCL and discusses future research directions toward molecular dissection of the pathogenesis of the disease and associated vision problems in order to ultimately improve the quality of patient life and cure the disease.

Citing Articles

Genetic and Cellular Basis of Impaired Phagocytosis and Photoreceptor Degeneration in CLN3 Disease.

Han J, Chear S, Talbot J, Swier V, Booth C, Reuben-Thomas C Invest Ophthalmol Vis Sci. 2024; 65(13):23.

PMID: 39535788 PMC: 11563035. DOI: 10.1167/iovs.65.13.23.

A novel pathogenic variant in the KCTD7 gene in a patient with neuronal ceroid lipofuscinosis (CLN14): a case report and review of the literature.

Zeineddin S, Matar G, Abosaif Y, Abunada M, Aldabbour B BMC Neurol. 2024; 24(1):367.

PMID: 39350080 PMC: 11441090. DOI: 10.1186/s12883-024-03868-w.

A recessive variant is responsible for delayed-onset retinal degeneration in Hereford cattle.

Reith R, Batt M, Fuller A, Meekins J, Diehl K, Zhou Y J Vet Diagn Invest. 2024; 36(3):438-446.

PMID: 38516801 PMC: 11110775. DOI: 10.1177/10406387241239918.

Early recognition of CLN3 disease facilitated by visual electrophysiology and multimodal imaging.

Sakti D, Cornish E, Fraser C, Nash B, Sandercoe T, Jones M Doc Ophthalmol. 2023; 146(3):241-256.

PMID: 36964447 PMC: 10256658. DOI: 10.1007/s10633-023-09930-1.

Lysosomal alterations and decreased electrophysiological activity in CLN3 disease patient-derived cortical neurons.

Chear S, Perry S, Wilson R, Bindoff A, Talbot J, Ware T Dis Model Mech. 2022; 15(12).

PMID: 36453132 PMC: 10655821. DOI: 10.1242/dmm.049651.

References

Pearce D, Ferea T, Nosel S, Das B, Sherman F . Action of BTN1, the yeast orthologue of the gene mutated in Batten disease. Nat Genet. 1999; 22(1):55-8. DOI: 10.1038/8861. View

HALL N, Lake B, Dewji N, PATRICK A . Lysosomal storage of subunit c of mitochondrial ATP synthase in Batten's disease (ceroid-lipofuscinosis). Biochem J. 1991; 275 ( Pt 1):269-72. PMC: 1150044. DOI: 10.1042/bj2750269. View

Wang F, Wang H, Tuan H, Nguyen D, Sun V, Keser V . Next generation sequencing-based molecular diagnosis of retinitis pigmentosa: identification of a novel genotype-phenotype correlation and clinical refinements. Hum Genet. 2013; 133(3):331-45. PMC: 3945441. DOI: 10.1007/s00439-013-1381-5. View

Autti T, Hamalainen J, Aberg L, Lauronen L, Tyynela J, Van Leemput K . Thalami and corona radiata in juvenile NCL (CLN3): a voxel-based morphometric study. Eur J Neurol. 2007; 14(4):447-50. DOI: 10.1111/j.1468-1331.2007.01692.x. View

Tecedor L, Stein C, Schultz M, Farwanah H, Sandhoff K, Davidson B . CLN3 loss disturbs membrane microdomain properties and protein transport in brain endothelial cells. J Neurosci. 2013; 33(46):18065-79. PMC: 3828460. DOI: 10.1523/JNEUROSCI.0498-13.2013. View

Pearce D . Localization and processing of CLN3, the protein associated to Batten disease: where is it and what does it do?. J Neurosci Res. 2000; 59(1):19-23. View

Das A, Kohlschutter A . Decreased activity of the mitochondrial ATP-synthase in fibroblasts from children with late-infantile and juvenile neuronal ceroid lipofuscinosis. J Inherit Metab Dis. 1996; 19(2):130-2. DOI: 10.1007/BF01799411. View

Dulz S, Wagenfeld L, Nickel M, Richard G, Schwartz R, Bartsch U . Novel morphological macular findings in juvenile CLN3 disease. Br J Ophthalmol. 2015; 100(6):824-8. DOI: 10.1136/bjophthalmol-2015-307320. View

LaVail M . Rods and cones in the mouse retina. I. Structural analysis using light and electron microscopy. J Comp Neurol. 1979; 188(2):245-62. DOI: 10.1002/cne.901880204. View

10.

Chattopadhyay S, Ito M, Cooper J, Brooks A, Curran T, Powers J . An autoantibody inhibitory to glutamic acid decarboxylase in the neurodegenerative disorder Batten disease. Hum Mol Genet. 2002; 11(12):1421-31. DOI: 10.1093/hmg/11.12.1421. View

11.

DYKEN P . Reconsideration of the classification of the neuronal ceroid-lipofuscinoses. Am J Med Genet Suppl. 1988; 5:69-84. DOI: 10.1002/ajmg.1320310610. View

12.

Pearce D, CARR C, Das B, Sherman F . Phenotypic reversal of the btn1 defects in yeast by chloroquine: a yeast model for Batten disease. Proc Natl Acad Sci U S A. 1999; 96(20):11341-5. PMC: 18035. DOI: 10.1073/pnas.96.20.11341. View

13.

Mitchison H, Bernard D, Greene N, Cooper J, Junaid M, Pullarkat R . Targeted disruption of the Cln3 gene provides a mouse model for Batten disease. The Batten Mouse Model Consortium [corrected]. Neurobiol Dis. 1999; 6(5):321-34. DOI: 10.1006/nbdi.1999.0267. View

14.

Biswas J, Nandi K, Sridharan S, Ranjan P . Ocular manifestation of storage diseases. Curr Opin Ophthalmol. 2008; 19(6):507-11. DOI: 10.1097/ICU.0b013e32831215c3. View

15.

Williams R, Mole S . New nomenclature and classification scheme for the neuronal ceroid lipofuscinoses. Neurology. 2012; 79(2):183-91. DOI: 10.1212/WNL.0b013e31825f0547. View

16.

Sappington R, Pearce D, Calkins D . Optic nerve degeneration in a murine model of juvenile ceroid lipofuscinosis. Invest Ophthalmol Vis Sci. 2003; 44(9):3725-31. DOI: 10.1167/iovs.03-0039. View

17.

Greene N, Bernard D, Taschner P, Lake B, De Vos N, Breuning M . A murine model for juvenile NCL: gene targeting of mouse Cln3. Mol Genet Metab. 1999; 66(4):309-13. DOI: 10.1006/mgme.1999.2828. View

18.

Cotman S, Karaa A, Staropoli J, Sims K . Neuronal ceroid lipofuscinosis: impact of recent genetic advances and expansion of the clinicopathologic spectrum. Curr Neurol Neurosci Rep. 2013; 13(8):366. PMC: 3774306. DOI: 10.1007/s11910-013-0366-z. View

19.

Golabek A, Kaczmarski W, Kida E, Kaczmarski A, Michalewski M, Wisniewski K . Expression studies of CLN3 protein (battenin) in fusion with the green fluorescent protein in mammalian cells in vitro. Mol Genet Metab. 1999; 66(4):277-82. DOI: 10.1006/mgme.1999.2836. View

20.

Conradi N, Uvebrant P, Hokegard K, Wahlstrom J, Mellqvist L . First-trimester diagnosis of juvenile neuronal ceroid lipofuscinosis by demonstration of fingerprint inclusions in chorionic villi. Prenat Diagn. 1989; 9(4):283-7. DOI: 10.1002/pd.1970090407. View