Expression of pigment epithelium-derived factor in normal adult rat eye and experimental choroidal neovascularization.
OBJECTIVE
Pigment epithelium-derived factor (PEDF) is a protein produced by the retinal pigment epithelial (RPE) cells. Recent studies have implicated PEDF in activities that are inhibitory to angiogenesis. In this study, the expression of PEDF was investigated in normal rat eyes and in eyes with experimentally induced choroidal neovascularization and compared with the expression of vascular endothelial growth factor (VEGF).


METHODS
Choroidal neovascularization was induced by laser photocoagulation in rat eyes. At intervals of up to 2 weeks after photocoagulation, the eyes were removed and prepared for in situ hybridization and immunohistochemical study. In situ hybridization was performed with digoxigenin-labeled PEDF riboprobes. Protein expression of PEDF and VEGF was studied immunohistochemically.


RESULTS
In normal adult rat eyes, PEDF mRNA was observed mainly in the corneal epithelial and endothelial cells, lens epithelial cells, ciliary epithelial cells, retinal ganglion cells, and the RPE cells. During the development of choroidal neovascularization, PEDF mRNA, PEDF protein, and VEGF protein were strongly detected in many cells within the laser lesions at 3 days after photocoagulation, after which levels gradually declined. However, PEDF was still expressed in the RPE cells that proliferated and covered the neovascular tissues at 2 weeks, whereas VEGF protein was weakly expressed in endothelial cells in choroidal neovascularization.


CONCLUSIONS
PEDF is expressed in different cell types of normal rat eyes. The expression of PEDF was detected in the choroidal neovascular tissues induced by photocoagulation, and these findings suggest that PEDF may modulate the process of choroidal neovascularization.
Ogata
Nahoko
N
Department of Ophthalmology, Kansai Medical University, Moriguchi, Osaka, Japan. ogata@takii.kmu.ac.jp
Wada
Mitsumasa
M
Otsuji
Tsuyoshi
T
Jo
Nobuo
N
Tombran-Tink
Joyce
J
Matsumura
Miyo
M
D000818:Animals; D020256:Choroidal Neovascularization / Q000378:metabolism* / Q000473:pathology; D003315:Cornea / Q000166:cytology / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D004728:Endothelium, Corneal / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D017075:Laser Coagulation; D007908:Lens, Crystalline / Q000166:cytology / Q000378:metabolism; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism; D009414:Nerve Growth Factors; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011914:Rats, Inbred BN; D012165:Retinal Ganglion Cells / Q000378:metabolism; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099174:Pigment Epithelium-Derived Factor
D016228:Endothelial Growth Factors; D005136:Eye Proteins; D008222:Lymphokines; D009414:Nerve Growth Factors; D011506:Proteins; D012333:RNA, Messenger; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099174:Pigment Epithelium-Derived Factor