Ocular wounding prevents pre-retinal neovascularization and upregulates PEDF expression in the inner retina.
OBJECTIVE
Perforation injury to the eye can protect against retinal degeneration and pigment epithelial derived factor (PEDF) may play a role in this neuro-protective effect. PEDF has also been shown to possess potent anti-angiogenic properties. The current study has investigated a possible anti-angiogenic effect of penetrating ocular injury in a murine model of oxygen induced proliferative retinopathy (OIR) and determined if such a procedure alters PEDF expression in the retina.


METHODS
OIR was produced by exposure of neonatal mice to 75% oxygen between postnatal days 7 and 12 (P7-P12). Mice were separated into various groups, with one group receiving a penetrating injury in a single eye. Pre-retinal neovascularization and intra-retinal ischaemia was quantified at P17 and PEDF protein expression was determined using immunofluorescence in retinal flatmounts and sections. PEDF mRNA was quantified using real-time RT-PCR.


RESULTS
Punctured eyes showed less pre-retinal neovascularization at P17 when compared to the non-punctured eyes (p<0.001) although there was no effect on retinal ischaemia. PEDF immunreactivity was strongest in the ganglion cells of the retina, and intensity increased in punctured eyes at P13. There was more immunoreactive PEDF in ganglion cells adjacent to retinal venules than arterioles. At P13, retinal PEDF mRNA was also increased in punctured eyes compared to non-punctured controls (p<0.05), although there was no differential at P17.


CONCLUSIONS
Penetrating ocular injury suppresses retinal neovascularization and modulates expression of PEDF. These findings have implications for intra-vitreal delivery of angiostatic agents since ocular perforation may provoke an acute, endogenous anti-angiogenic response that should be taken into account.
Stitt
Alan W
AW
Ophthalmic Research Centre, Queen's University Belfast, Institute of Clinical Sciences, Royal Victoria Hospital, Belfast, Northern Ireland, UK. a.stitt@qub.ac.uk
Graham
Donna
D
Gardiner
Tom A
TA
D000818:Animals; D000831:Animals, Newborn; D002924:Ciliary Body / Q000293:injuries; D004195:Disease Models, Animal; D015807:Eye Injuries, Penetrating / Q000150:complications* / Q000378:metabolism; D005136:Eye Proteins; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D018496:Hyperoxia / Q000150:complications; D007231:Infant, Newborn; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors; D010100:Oxygen / Q000633:toxicity; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D015861:Retinal Neovascularization / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D012178:Retinopathy of Prematurity / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014822:Vitreous Body / Q000293:injuries; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D010100:Oxygen; D011506:Proteins; D012333:RNA, Messenger; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor