The Genomic, Biochemical, and Cellular Responses of the Retina in Inherited Photoreceptor Degenerations and Prospects for the Treatment of These Disorders

被引：128

作者：

Bramall, Alexa N. ^{[1
,2
,3
]}

Wright, Alan F. ^{[5
]}

Jacobson, Samuel G. ^{[6
]}

McInnes, Roderick R. ^{[1
,2
,3
,4
]}

机构：

[1] Hosp Sick Children, Program Genet, Res Inst, Toronto, ON M5G 1L7, Canada

[2] Hosp Sick Children, Program Dev Biol, Res Inst, Toronto, ON M5G 1L7, Canada

[3] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada

[4] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada

[5] Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[6] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA

来源：

ANNUAL REVIEW OF NEUROSCIENCE, VOL 33 | 2010年 / 33卷

基金：

英国医学研究理事会;

关键词：

retinal degeneration; pathogenesis of photoreceptor death; genomic; biochemical; and cellular responses to mutation; human histology; gene therapy; CILIARY NEUROTROPHIC FACTOR; LEBER CONGENITAL AMAUROSIS; LEUKEMIA INHIBITORY FACTOR; FIBRILLARY ACIDIC PROTEIN; THERAPY RESTORES VISION; BCL-2; FAMILY-MEMBERS; HUMAN GENE-THERAPY; MULLER CELLS; MACULAR DYSTROPHY; USHER-SYNDROME;

D O I：

10.1146/annurev-neuro-060909-153227

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The association of more than 140 genes with human photoreceptor degenerations, together with studies of animal models of these monogenic diseases, has provided great insight into their pathogenesis. Here we review the responses of the retina to photoreceptor mutations, including mechanisms of photoreceptor death. We discuss the roles of oxidative metabolism, mitochondrial reactive oxygen species, metabolic stress, protein misfolding, and defects in ciliary proteins, as well as the responses of Muller glia, microglia, and the retinal vasculature. Finally, we report on potential pharmacologic and biologic therapies, the critical role of histopathology as a prerequisite to treatment, and the exciting promise of gene therapy in animal models and in phase I trials in humans.

引用

页码：441 / 472

页数：32

共 216 条

[41] Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man [J].

Cideciyan, AV ;

Hood, DC ;

Huang, YJ ;

Banin, E ;

Li, ZY ;

Stone, EM ;

Milam, AH ;

Jacobson, SG .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (12) :7103-7108

[42] In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa [J].

Cideciyan, AV ;

Jacobson, SG ;

Aleman, TS ;

Gu, DN ;

Pearce-Kelling, SE ;

Sumaroka, A ;

Acland, GM ;

Aguirre, GD .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (14) :5233-5238

[43] A one-hit model of cell death in inherited neuronal degenerations [J].

Clarke, G ;

Collins, RA ;

Leavitt, BR ;

Andrews, DF ;

Hayden, MR ;

Lumsden, CJ ;

McInnes, RR .

NATURE, 2000, 406 (6792) :195-199

[44] Scale-free neurodegeneration: cellular heterogeneity and the stretched exponential kinetics of cell death [J].

Clarke, G ;

Lumsden, CJ .

JOURNAL OF THEORETICAL BIOLOGY, 2005, 233 (04) :515-525

[45] Apoptotic morphology of dentate gyrus granule cells following experimental cortical impact injury in rats: Possible role in spatial memory deficits [J].

Colicos, MA ;

Dash, PK .

BRAIN RESEARCH, 1996, 739 (1-2) :120-131

[46] Biological characterization of gene response in Rpe65-/- mouse model of Leber's congenital amaurosis during progression of the disease [J].

Cottet, Sandra ;

Michaut, Lydia ;

Boisset, Gaeelle ;

Schlecht, Ulrich ;

Gehring, Walter ;

Schorderet, Daniel F. .

FASEB JOURNAL, 2006, 20 (12) :2036-2049

[47] Perspective on genes and mutations causing retinitis pigmentosa [J].

Daiger, Stephen P. ;

Bowne, Sara J. ;

Sullivan, Lori S. .

ARCHIVES OF OPHTHALMOLOGY, 2007, 125 (02) :151-158

[48] Muller glia as an active compartment modulating nervous activity in the vertebrate retina: Neurotransmitters and trophic factors [J].

de Melo Reis, Ricardo Augusto ;

Marques Ventura, Ana Lucia ;

Schitine, Clarissa Sampaio ;

Fialho de Mello, Maria Christina ;

de Mello, Fernando Garcia .

NEUROCHEMICAL RESEARCH, 2008, 33 (08) :1466-1474

[49] Disease mechanism for retinitis pigmentosa (RP11) caused by mutations in the splicing factor gene PRPF31 [J].

Deery, EC ;

Vithana, EN ;

Newbold, RJ ;

Gallon, VA ;

Bhattacharya, SS ;

Warren, MJ ;

Hunt, DM ;

Wilkie, SE .

HUMAN MOLECULAR GENETICS, 2002, 11 (25) :3209-3219

[50] In utero gene therapy rescues vision in a murine model of congenital blindness [J].

Dejneka, NS ;

Surace, EM ;

Aleman, TS ;

Cideciyan, AV ;

Lyubarsky, A ;

Savchenko, A ;

Redmond, TM ;

Tang, WX ;

Wei, ZY ;

Rex, TS ;

Glover, E ;

Maguire, AM ;

Pugh, EN ;

Jacobson, SG ;

Bennett, J .

MOLECULAR THERAPY, 2004, 9 (02) :182-188

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