Early activation of inflammation- and immune response-related genes after experimental detachment of the porcine retina.
OBJECTIVE
To determine early alterations in retinal gene expression in a porcine model of rhegmatogenous retinal detachment.


METHODS
Local detachment was created in eyes of adult pigs by subretinal application of sodium hyaluronate. The gene expression in control tissues and retinas detached for 24 hours was analyzed with a pig genome microarray. Genes with at least three-fold expression changes were detected in the detached retina and in the attached retinal tissue surrounding the local detachment in situ. Structural alterations of the retina were examined by light and electron microscopy.


RESULTS
Identified were 85 genes that were upregulated and 7 that were downregulated in the detached retina. Twenty-eight genes were identified as upregulated in the nondetached retina of the surgical eyes. The genes upregulated in detached retinas were related to inflammation and immune responses (n = 52), antioxidants and metal homeostasis (n = 7), intracellular proteolysis (n = 6), and blood coagulation/fibrinolysis (n = 4). The upregulation of at least 15 interferon-stimulated genes indicates elevated interferon levels after detachment. Gene expression of blue-sensitive opsin was not detectable in the detached retinal tissue, suggesting an early reduction in phototransduction, especially in blue cones. Electron microscopy revealed an accumulation of microglial cells in the inner retinal tissue and of polymorphonuclear leukocytes in the vessels of detached and peridetached retinas.


CONCLUSIONS
Differentially expressed genes in the retina early after experimental detachment are mainly related to inflammation and immune responses, intracellular proteolysis, and protection against oxidative stress. A local immune and inflammatory response may represent a major causative factor for reactive changes in the retina after detachment. The inflammatory response is not restricted to the detached retina but is also observed in the nondetached retina; this response may underlie functional changes in these regions described in human subjects.
Hollborn
Margrit
M
Department of Ophthalmology and Eye Clinic, Interdisciplinary Center of Clinical Research (IZKF), University of Leipzig Faculty of Medicine, Leipzig, Germany.
Francke
Mike
M
Iandiev
Ianors
I
Bühner
Eva
E
Foja
Christian
C
Kohen
Leon
L
Reichenbach
Andreas
A
Wiedemann
Peter
P
Bringmann
Andreas
A
Uhlmann
Susann
S
D000818:Animals; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000502:physiology; D020869:Gene Expression Profiling; D005802:Genes, MHC Class II / Q000502:physiology*; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D012160:Retina / Q000378:metabolism* / Q000648:ultrastructure; D012163:Retinal Detachment / Q000235:genetics* / Q000473:pathology; D012173:Retinitis / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D015854:Up-Regulation
D005136:Eye Proteins