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RC Ilg; Retinal Neovascularization Is Altered In Tnf Receptor Deficient Mice In Oxygen-induced Retinopathy . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2744.
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Purpose: Tumor necrosis factor (TNF-α) has been shown to play an integral role in inflammation, neovascularization, and apoptosis. We explored the role of TNF-α in retinal vaso-obliteration and neovascularization in mice lacking the 55-kd and 75-kd receptors for TNF-α. Methods: On postnatal day 7 (P7) TNFR p55-/-p75-/- and congenic B6129JF1 mice were exposed to 75% oxygen for up to 5 days and then recovered in room air. Eyes were obtained on P7, P8, P10, P12, P14, P17 and P21 for histopathologic examination. Retinopathy was qualitatively assessed in FITC-dextran perfused retinas by fluorescence microscopy. Retinopathy was also quantitated by counting preretinal neovascular nuclei on P17 and P21. Intraretinal blood vessel formation was quantitated by immunolabeling vessels with an anti-type IV collagen antibody. Results: TNFR p55-/-p75-/- and B6129JF1 mice qualitatively exhibited similar retinal development. Additionally, the FITC-dextran perfused eyes revealed a similar degree of vaso-obliteration on P12 in the mice after oxygen exposure. By P17, the oxygen exposed mice developed neovascular tufts in both the TNFR p55-/-p75-/- and B6129JF1 control animals. The average number of preretinal nuclei counted on P17 in the TNFR p55-/-p75-/- mice and the B6129JF1 control mice was approximately 33 nuclei per section. However, by P21 the TNFR p55-/-p75-/- mice continued to exhibit extensive neovascular tufts and areas of vaso-obliteration. The average number of preretinal nuclei in the TNFR p55-/-p75-/- was approximately 28 nuclei per section on P21, while the average in the B6129JF1 controls had decreased to approximately 6 nuclei per section. Type IV collagen staining of intraretinal vessels showed a decreased number of vessels in the oxygen-exposed TNFR p55-/-p75-/- as compared to the oxygen-exposed controls on days P14, P17 and P21. Conclusion: TNFR p55-/-p75-/- mice, as compared to their congenic control, develop similar neovascularization on P17. However, by P21, the TNFR p55-/-p75-/- mice continue to exhibit a large number of tufts and preretinal nuclei suggesting more severe retinopathy. This may be due to an altered response to vaso-obliteration or a decreased ability to remodel or control the degree of neovascularization. These results suggest that TNF-α plays a role in retinal neovascularization and blood vessel remodeling.
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