Proliferative vitreoretinopathy in the Swine-a new model.
OBJECTIVE
To develop a large animal model of proliferative vitreoretinopathy (PVR) in the swine to eventually study disease pathophysiology, as well as novel therapies.


METHODS
PVR was induced in domestic swine by creation of a posterior vitreous detachment, creation of a retinal detachment by the injection of subretinal fluid, and intravitreal injection of green fluorescent protein-positive retinal pigment epithelial (GFP+ RPE) cells. Control eyes had the same surgical procedures without RPE cell injection. PVR was clinically graded on days 3, 7, and 14. Animals were euthanized on day 14, and enucleated eyes were analyzed by light microscopy and immunohistochemistry.


RESULTS
Injection of GFP+ RPE cells into the vitreous cavity produced localized, traction retinal detachments by day 14 in all eyes (14 of 14); in contrast, the retina spontaneously reattached by day 3 and remained attached in all control eyes (10 of 10). Contractile epiretinal membranes on the inner retinal surface that caused the traction retinal detachments consisted predominantly of GFP+ RPE cells. These cells stained positive for cytokeratin, confirming their epithelial origin, and also expressed α-SMA and fibronectin, markers for myofibroblasts and fibrosis, respectively.


CONCLUSIONS
We established a swine PVR model that recapitulates key clinical features found in humans and, thus, can be used to study the pathophysiology of PVR, as well as new novel therapies. GFP+ RPE cells injected into the vitreous cavity formed contractile membranes on the inner retinal surface and caused localized traction retinal detachments.
Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY, USA.
Kazuhiko
K
Umazume
Yoreh
Y
Barak
Kevin
K
McDonald
Lanhsin
L
Liu
Henry J
HJ
Kaplan
Shigeo
S
Tamiya
D000199:Actins / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D019773:Epiretinal Membrane / Q000503:physiopathology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis / Q000503:physiopathology; D049452:Green Fluorescent Proteins / Q000633:toxicity*; D007633:Keratins / Q000378:metabolism; D049408:Luminescent Agents / Q000633:toxicity*; D058628:Myofibroblasts / Q000473:pathology; D012160:Retina / Q000503:physiopathology* / Q000601:surgery; D012163:Retinal Detachment / Q000139:chemically induced*; D055213:Retinal Pigment Epithelium; D013552:Swine; D018630:Vitreoretinopathy, Proliferative / Q000209:etiology* / Q000503:physiopathology
D000199:Actins; D005353:Fibronectins; D049408:Luminescent Agents; D049452:Green Fluorescent Proteins; D007633:Keratins