Protein changes in the retina following experimental retinal detachment in rabbits

TY - JOUR

T1 - Protein changes in the retina following experimental retinal detachment in rabbits

AU - Mandal, Nakul

AU - Lewis, Geoffrey P

AU - Fisher, Steven K

AU - Heegaard, Steffen

AU - Prause, Jan U

AU - la Cour, Morten

AU - Vorum, Henrik

AU - Honoré, Bent

PY - 2011/10/8

Y1 - 2011/10/8

N2 - Purpose: Retinal detachment leads to the widespread cellular remodeling of the retina. The purpose of this study was to identify protein changes that accompany these cellular alterations by comparing the proteomic profiles of sham and experimentally detached rabbit retina. Elucidation of the proteins most dramatically affected by retinal detachment would add further understanding to the pathophysiology of this condition, and potentially identify therapeutic targets useful in preventing the deleterious effects of detachment, including photoreceptor cell death and the activation of non-neuronal microglial and Müller cells. Methods: Retinal detachments were induced in the right eyes of six New Zealand Red pigmented rabbits. Sham surgery was performed in the right eyes of six other rabbits that were used as controls. At seven days, the eyes were enucleated and the retinal tissue was harvested. The individual retinal samples were subjected to high resolution two-dimensional polyacrylamide gel electrophoresis. Differentially expressed protein spots were processed for identification by liquid chromatography-tandem mass spectrometry. Further investigation was undertaken with western blotting, and immunocytochemical studies on a further set of four sham and four detached retinas. Results: Eighteen protein spots were found to be at least twofold differentially expressed between the sham and detached retinas. These protein spots were identified as: vimentin; tubulin β-2C; fragments of α-enolase; fructose-bisphosphate aldolase A; ATP synthase subunit β; mitochondrial creatine kinase; N-terminal fragments of albumin; prohibitin; and transducin-β1. Conclusions: The differentially expressed proteins determined in this study may play an important role in the cellular responses of the retina after its detachment, subsequent ability to recover following surgical reattachment, as well as in serious complications such as subretinal fibrosis and proliferative vitreoretinopathy.

AB - Purpose: Retinal detachment leads to the widespread cellular remodeling of the retina. The purpose of this study was to identify protein changes that accompany these cellular alterations by comparing the proteomic profiles of sham and experimentally detached rabbit retina. Elucidation of the proteins most dramatically affected by retinal detachment would add further understanding to the pathophysiology of this condition, and potentially identify therapeutic targets useful in preventing the deleterious effects of detachment, including photoreceptor cell death and the activation of non-neuronal microglial and Müller cells. Methods: Retinal detachments were induced in the right eyes of six New Zealand Red pigmented rabbits. Sham surgery was performed in the right eyes of six other rabbits that were used as controls. At seven days, the eyes were enucleated and the retinal tissue was harvested. The individual retinal samples were subjected to high resolution two-dimensional polyacrylamide gel electrophoresis. Differentially expressed protein spots were processed for identification by liquid chromatography-tandem mass spectrometry. Further investigation was undertaken with western blotting, and immunocytochemical studies on a further set of four sham and four detached retinas. Results: Eighteen protein spots were found to be at least twofold differentially expressed between the sham and detached retinas. These protein spots were identified as: vimentin; tubulin β-2C; fragments of α-enolase; fructose-bisphosphate aldolase A; ATP synthase subunit β; mitochondrial creatine kinase; N-terminal fragments of albumin; prohibitin; and transducin-β1. Conclusions: The differentially expressed proteins determined in this study may play an important role in the cellular responses of the retina after its detachment, subsequent ability to recover following surgical reattachment, as well as in serious complications such as subretinal fibrosis and proliferative vitreoretinopathy.

KW - Animals

KW - Blotting, Western

KW - Chromatography, Liquid

KW - Disease Models, Animal

KW - Electrophoresis, Gel, Two-Dimensional

KW - Eye Proteins

KW - Gene Expression Profiling

KW - Proteomics

KW - Rabbits

KW - Retina

KW - Retinal Detachment

KW - Tandem Mass Spectrometry

M3 - Journal article

C2 - 22065916

SN - 1090-0535

VL - 17

SP - 2634

EP - 2648

JO - Molecular Vision

JF - Molecular Vision

ER -