Angiostatic effect of penetrating ocular injury: role of pigment epithelium-derived factor.
OBJECTIVE
To characterize the angiostatic effect of penetrating ocular injury and to begin to explore its mechanism, with an emphasis on the role of pigment epithelium-derived factor (PEDF).


METHODS
Using the rat model of oxygen-induced retinopathy (OIR), single or multiple dry needle injuries were made, penetrating the globe of one eye; the opposite eye served as a control. Eyes were harvested from rats killed 1, 3, and 6 days after injury, and retinas were dissected and processed for assessment of neovascularization and microglial activation or were processed for genetic and proteomic analysis. Temporal and spatial expression patterns of PEDF were analyzed by in situ hybridization.


RESULTS
Penetrating ocular injury resulted in a 30% decrease in neovascular area in the retinas of OIR rats. At day 1 after injury, needle insertion caused a 4.1-fold increase in retinal PEDF mRNA and a 1.5-fold increase in retinal PEDF protein. Vitreous PEDF protein increased 3.4-fold in injured eyes compared with noninjured eyes. In situ hybridization showed an increase in PEDF mRNA in areas surrounding the puncture site. Concentrated vitreous protein from injured eyes caused a 60% decrease in retinal neovascularization when injected into the vitreous cavity of OIR rats. Preincubation of vitreous samples with anti-PEDF partially abolished this efficacy.


CONCLUSIONS
The pattern of angiostasis resulting from penetrating ocular injury is consistent with the release of an endogenous antiangiogenic factor from the wound site. Preliminary studies show a possible role for PEDF in this effect. Further characterization of this role and the identification of other factors may lead to new therapeutic strategies for angiogenic eye conditions.
Penn
John S
JS
Department of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-8808, USA. john.penn@vanderbilt.edu
McCollum
Gary W
GW
Barnett
Joshua M
JM
Werdich
Xiang Q
XQ
Koepke
Katherine A
KA
Rajaratnam
Veera S
VS
D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D015807:Eye Injuries, Penetrating / Q000378:metabolism*; D005136:Eye Proteins / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D017403:In Situ Hybridization; D009414:Nerve Growth Factors / Q000502:physiology*; D009457:Neuroglia / Q000473:pathology; D010100:Oxygen / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000293:injuries* / Q000378:metabolism; D015861:Retinal Neovascularization / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000502:physiology*; D014822:Vitreous Body / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
D020533:Angiogenesis Inhibitors; D005136:Eye Proteins; D009414:Nerve Growth Factors; D010100:Oxygen; D012333:RNA, Messenger; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor