Retinal degeneration is delayed by tissue factor pathway inhibitor-2 in RCS rats and a sodium-iodate-induced model in rabbits.
OBJECTIVE
To investigate the in vivo effects of tissue factor pathway inhibitor 2 (TFPI-2), which stimulates proliferation of retinal pigment epithelial cells, but not the proliferation of fibroblast and vascular endothelial cells in vitro, on retinal degeneration using a sodium-iodate (SI)-induced model in rabbits and Royal Collage of Surgeons (RCS) rats.


METHODS
79 microg of recombinant TFPI-2 (rTFPI-2) or vehicle alone was injected intravitreously to 18 eyes of 12 pigmented rabbits a day after 20 mg/kg of SI was intravenously administered. Retinal function was assessed 4, 7, 14, and 21 days after the injection by analysing amplitudes of the c-wave of a bright flash electroretinogram. Additionally, 10 microg of rTFPI-2 or vehicle alone was injected intravitreously to 11 eyes of RCS rats at both 3 and 4 weeks old, then the retina was examined histologically at 5 weeks old.


RESULTS
The rTFPI-2-treated eyes in rabbits showed a significantly less decrease in the relative amplitude of the c-wave than control eyes on days 4 and 7. The thickness of the outer nuclear layer was significantly thicker and the vacuole in the photoreceptor layer was less frequently observed in the rTFPI-2-treated RCS rats than the controls.


CONCLUSIONS
Intravitreal injection of TFPI-2 rescues SI-induced retinal degeneration in rabbits and naturally occurring retinal degeneration in RCS rats at least partly. These results may suggest that this compound can be utilized in the treatment of retinal degeneration.
Obata
R
R
Department of Ophthalmology, University of Tokyo, School of Medicine, Bunkyo-ku, Tokyo, Japan. robata-tky@umin.ac.jp
Yanagi
Y
Y
Tamaki
Y
Y
Hozumi
K
K
Mutoh
M
M
Tanaka
Y
Y
D000818:Animals; D004195:Disease Models, Animal; D004596:Electroretinography; D006023:Glycoproteins / Q000627:therapeutic use*; D007267:Injections; D007452:Iodates; D008297:Male; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000473:pathology; D011817:Rabbits; D011994:Recombinant Proteins / Q000627:therapeutic use; D012162:Retinal Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D014822:Vitreous Body
D006023:Glycoproteins; D007452:Iodates; D011994:Recombinant Proteins; C021240:tissue-factor-pathway inhibitor 2; C032285:sodium iodate