TY - JOUR
T1 - Increased retinal neovascularization in Fas ligand-deficient mice
AU - Davies, Michael H.
AU - Eubanks, Joshua P.
AU - Powers, Michael R.
PY - 2003/7/1
Y1 - 2003/7/1
N2 - PURPOSE. To investigate whether the absence of the Fas-Fas ligand system of apoptosis regulation affects hyperoxia-induced retinal vaso-obliteration and retinal neovascularization in a mouse model of oxygen-induced retinopathy. METHODS. C57BL/6 (B6) and congenic Fas ligand-deficient generalized lymphoproliferative disease (gld) mice were exposed to 75% oxygen from postnatal day (P)7 to P12 and then allowed to recover in room air. Eyes obtained from P7, P8, P10, P12, P14, P17, and P21, from both hyperoxia-injured and room air control animals were processed for histopathologic examination. Retinopathy was also qualitatively assessed in FITC-dextran perfused retinas by fluorescence microscopy. TUNEL assays were used to compare apoptosis in B6 and gld mice. Intraretinal blood vessel formation was quantitated by immunolabeling with an anti-type-IV collagen antibody. Retinopathy was further assessed by quantitation of preretinal neovascular nuclei on P17. RT-PCR was used to examine retinal expression of Fas and Fas ligand (FasL) over a time course of hyperoxia-induced retinopathy. RESULTS. In hyperoxia-injured mice, the same degree of vaso-obliteration was apparent on P8, P10, and P12 in B6 and gld mice. By P17, the hyperoxia-exposed FITC-perfused retinas of both strains exhibited preretinal neovascular tufts. However, P17 gld hyperoxia-exposed retinas exhibited approximately a 50% increase in preretinal neovascular nuclei compared with B6 mice. In addition, a subset of apoptotic cells located solely within the neovascular tufts on P17 were significantly decreased in hyperoxia-exposed gld retinas, compared with B6 control animals. RT-PCR showed an increase in the expression levels of Fas in both strains of mice as a result of hyperoxia-induced injury. CONCLUSIONS. These data suggest that the Fas-FasL interaction plays an important role in retinal neovascularization after hyperoxia-induced injury. The absence of functional FasL leads to an increased incidence of preretinal neovascular nuclei and decreased retinal apoptosis suggesting that this pathway may serve as a means of regulating endogenous endothelial cell populations in pathologic angiogenesis.
AB - PURPOSE. To investigate whether the absence of the Fas-Fas ligand system of apoptosis regulation affects hyperoxia-induced retinal vaso-obliteration and retinal neovascularization in a mouse model of oxygen-induced retinopathy. METHODS. C57BL/6 (B6) and congenic Fas ligand-deficient generalized lymphoproliferative disease (gld) mice were exposed to 75% oxygen from postnatal day (P)7 to P12 and then allowed to recover in room air. Eyes obtained from P7, P8, P10, P12, P14, P17, and P21, from both hyperoxia-injured and room air control animals were processed for histopathologic examination. Retinopathy was also qualitatively assessed in FITC-dextran perfused retinas by fluorescence microscopy. TUNEL assays were used to compare apoptosis in B6 and gld mice. Intraretinal blood vessel formation was quantitated by immunolabeling with an anti-type-IV collagen antibody. Retinopathy was further assessed by quantitation of preretinal neovascular nuclei on P17. RT-PCR was used to examine retinal expression of Fas and Fas ligand (FasL) over a time course of hyperoxia-induced retinopathy. RESULTS. In hyperoxia-injured mice, the same degree of vaso-obliteration was apparent on P8, P10, and P12 in B6 and gld mice. By P17, the hyperoxia-exposed FITC-perfused retinas of both strains exhibited preretinal neovascular tufts. However, P17 gld hyperoxia-exposed retinas exhibited approximately a 50% increase in preretinal neovascular nuclei compared with B6 mice. In addition, a subset of apoptotic cells located solely within the neovascular tufts on P17 were significantly decreased in hyperoxia-exposed gld retinas, compared with B6 control animals. RT-PCR showed an increase in the expression levels of Fas in both strains of mice as a result of hyperoxia-induced injury. CONCLUSIONS. These data suggest that the Fas-FasL interaction plays an important role in retinal neovascularization after hyperoxia-induced injury. The absence of functional FasL leads to an increased incidence of preretinal neovascular nuclei and decreased retinal apoptosis suggesting that this pathway may serve as a means of regulating endogenous endothelial cell populations in pathologic angiogenesis.
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U2 - 10.1167/iovs.03-0050
DO - 10.1167/iovs.03-0050
M3 - Article
C2 - 12824272
AN - SCOPUS:0037900474
SN - 0146-0404
VL - 44
SP - 3202
EP - 3210
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 7
ER -