Chronically shortened rod outer segments accompany photoreceptor cell death in Choroideremia.

PloS One
Ingrid P MeschedeClare E Futter

Abstract

X-linked choroideremia (CHM) is a disease characterized by gradual retinal degeneration caused by loss of the Rab Escort Protein, REP1. Despite partial compensation by REP2 the disease is characterized by prenylation defects in multiple members of the Rab protein family that are master regulators of membrane traffic. Remarkably, the eye is the only organ affected in CHM patients, possibly because of the huge membrane traffic burden of the post mitotic photoreceptors, which synthesise outer segments, and the adjacent retinal pigment epithelium that degrades the spent portions each day. In this study, we aimed to identify defects in membrane traffic that might lead to photoreceptor cell death in CHM. In a heterozygous null female mouse model of CHM (Chmnull/WT), degeneration of the photoreceptor layer was clearly evident from increased numbers of TUNEL positive cells compared to age matched controls, small numbers of cells exhibiting signs of mitochondrial stress and greatly increased microglial infiltration. However, most rod photoreceptors exhibited remarkably normal morphology with well-formed outer segments and no discernible accumulation of transport vesicles in the inner segment. The major evidence of membrane trafficking d...Continue Reading

References

Apr 1, 1980·The Journal of Comparative Neurology·R H SteinbergD H Anderson
Oct 13, 1995·The Journal of Biological Chemistry·M C SeabraJ S Anant
Jan 1, 1995·Eye·C J KennedyI J Constable
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·T LiT P Dryja
Feb 1, 1997·Nature Genetics·M M HumphriesP Humphries
Jan 20, 1999·Proceedings of the National Academy of Sciences of the United States of America·J LemR L Sidman
Nov 18, 2003·Molecular Biology of the Cell·Tanya TolmachovaMiguel C Seabra
Feb 24, 2004·Molecular Biology of the Cell·Clare E FutterMiguel C Seabra
Feb 27, 2004·Investigative Ophthalmology & Visual Science·Caroline J Zeiss, Elizabeth A Johnson
Aug 29, 2006·Investigative Ophthalmology & Visual Science·Samuel G JacobsonIan M MacDonald
Nov 23, 2006·Lancet·Dyonne T HartongThaddeus P Dryja
Jul 21, 2007·Visual Neuroscience·Alexander Cunea, Glen Jeffery
May 9, 2009·Survey of Ophthalmology·Ian M MacDonaldChi-Chao Chan
Jul 16, 2009·Nature Reviews. Molecular Cell Biology·Harald Stenmark
May 7, 2010·Investigative Ophthalmology & Visual Science·Tanya TolmachovaMiguel C Seabra
Sep 19, 2012·Ophthalmology·Noriko YoshidaTatsuro Ishibashi
Sep 19, 2012·Ophthalmology·Noriko YoshidaTatsuro Ishibashi
Oct 19, 2013·Progress in Retinal and Eye Research·Jing Wang, Dusanka Deretic
Dec 21, 2013·PloS One·Monika KöhnkeKirill Alexandrov
Oct 2, 2014·Molecular Neurobiology·Wei-Chieh ChiangJonathan H Lin
Jun 10, 2015·Progress in Molecular Biology and Translational Science·Ina NemetYoshikazu Imanishi
Nov 4, 2015·The Journal of Cell Biology·Jin-Dong DingVadim Y Arshavsky
Nov 19, 2015·Proceedings of the National Academy of Sciences of the United States of America·Stefanie VollandDavid S Williams

❮ Previous
Next ❯

Citations

Jul 14, 2021·Translational Vision Science & Technology·Lewis E FryRobert E MacLaren

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPases
genotyping
electron microscopy
transmission electron microscopy

Software Mentioned

ImageJ

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.