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Retinal degeneration is delayed by tissue factor pathway inhibitor-2 in RCS rats and a sodium-iodate-induced model in
1Department of Ophthalmology, University of Tokyo, School of Medicine, Bunkyo-ku, Tokyo, Japan. robata-tky@umin.ac.jp
Purpose:
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.
Insights
Tissue Factor Pathway Inhibitor 2 (TFPI-2) intravitreal injections protected against retinal degeneration in rabbit and rat models. TFPI-2 treatment preserved retinal function and structure, suggesting potential therapeutic applications for vision loss.
Area of Science:
- Ophthalmology
- Regenerative Medicine
- Molecular Biology
Background:
- Retinal degeneration leads to vision loss.
- Tissue Factor Pathway Inhibitor 2 (TFPI-2) promotes retinal pigment epithelial cell proliferation in vitro.
- The in vivo effects of TFPI-2 on retinal degeneration are unknown.
Purpose of the Study:
- To investigate the in vivo therapeutic potential of TFPI-2 in models of retinal degeneration.
- To assess the effects of TFPI-2 on sodium-iodate (SI)-induced retinal damage in rabbits.
- To evaluate TFPI-2's impact on naturally occurring retinal degeneration in Royal College of Surgeons (RCS) rats.
Main Methods:
- Intravitreal injection of recombinant TFPI-2 (rTFPI-2) or vehicle into rabbit eyes after SI administration.
- Assessment of retinal function using electroretinography (c-wave amplitude) in rabbits.
- Intravitreal injection of rTFPI-2 or vehicle into RCS rats, followed by histological examination of retinal structure.
Main Results:
- rTFPI-2 treatment significantly reduced the decrease in c-wave amplitude in SI-treated rabbits.
- rTFPI-2-treated RCS rats exhibited a thicker outer nuclear layer compared to controls.
- Vacuole formation in the photoreceptor layer was less frequent in rTFPI-2-treated RCS rats.
Conclusions:
- Intravitreal TFPI-2 administration partially rescues SI-induced retinal degeneration in rabbits.
- TFPI-2 treatment also mitigates naturally occurring retinal degeneration in RCS rats.
- TFPI-2 shows promise as a potential therapeutic agent for treating retinal degeneration.
