In vivo protection of photoreceptors from light damage by pigment epithelium-derived factor.
OBJECTIVE
To determine whether pigment epithelium-derived factor (PEDF) exhibits neurotrophic and neuroprotective activities in vivo for photoreceptor cells.


METHODS
Sprague-Dawley albino rats were injected intravitreally with 2 microg PEDF or a mixture of 1 microg basic fibroblast growth factor (bFGF)/1 microg PEDF in a volume of 1 microl phosphate-buffered saline (PBS). Animals were exposed to constant light for different periods at an illuminance level of 1200 to 1500 lux. The electroretinogram (ERG) waveforms of both eyes in the same animal were simultaneously recorded to evaluate functional protection. The morphologic protection was evaluated by quantitative histology.


RESULTS
Intravitreal injection of PEDF before exposure to constant light resulted in significant morphologic and functional protection of photoreceptor cells in the retina of light-damaged rats. This protection depended on the duration and severity of light damage. The protection was eliminated by extending the light exposure to 10 days. Injection of PEDF at 0, 1, and 2 days after constant light exposure did not provide significant protection above that seen in PBS-injected eyes. Combination of PEDF with bFGF improved functional protection of photoreceptor cells.


CONCLUSIONS
The data demonstrate that PEDF protected photoreceptor cells against light damage. This is significant, because it may open new avenues for the study of molecular mechanisms underlying degenerative processes. This, in turn, may lead to the development of therapeutic strategies for the prevention and treatment of degenerative diseases of the retina.
Cao
W
W
Department of Ophthalmology, Health Science Center, Dean McGee Eye Institute, University of Oklahoma, Oklahoma City 73104, USA. wei-cao@ouhsc.edu
Tombran-Tink
J
J
Elias
R
R
Sezate
S
S
Mrazek
D
D
McGinnis
J F
JF
D000818:Animals; D004338:Drug Combinations; D004596:Electroretinography; D005136:Eye Proteins / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007267:Injections; D008027:Light / Q000009:adverse effects*; D009414:Nerve Growth Factors; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D011506:Proteins / Q000494:pharmacology*; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D015843:Serpins / Q000494:pharmacology*; D014822:Vitreous Body; D000099174:Pigment Epithelium-Derived Factor
D004338:Drug Combinations; D005136:Eye Proteins; D016222:Fibroblast Growth Factor 2; D009414:Nerve Growth Factors; D011506:Proteins; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor