May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
TNF Receptor Deficient Mice Exhibit An Altered Apoptotic and Glial Response During Oxygen–Induced Retinopathy.
Author Affiliations & Notes
  • M.H. Davies
    Pediatrics and Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR
  • R.C. Ilg
    Pediatrics and Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR
  • M.R. Powers
    Pediatrics and Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR
  • Footnotes
    Commercial Relationships  M.H. Davies, None; R.C. Ilg, None; M.R. Powers, None.
  • Footnotes
    Support  NIH EY011548 & Research to Prevent Blindness
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 1906. doi:
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      M.H. Davies, R.C. Ilg, M.R. Powers; TNF Receptor Deficient Mice Exhibit An Altered Apoptotic and Glial Response During Oxygen–Induced Retinopathy. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1906.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Tumor necrosis factor–alpha (TNF–α) can induce inflammation, promote apoptosis, and modulate angiogenesis. We previously reported prolonged neovascularization (NV) in mice lacking 55–kd and 75–kd receptors for TNF–α (TNFR–) (Ilg RC, IOVS 2002;43:ARVO E–Abstract 2744). The present study was performed to determine if altered apoptosis or enhanced glial cell response contributes to the prolonged NV observed in TNFR– mice. Methods: Postnatal day (P)7 TNFR– mice and congenic B6129J (B6) mice were exposed to 75% oxygen for up to 5 days (P12), and then recovered in room air. Eyes from oxygen–exposed (O2) mice and unexposed controls were obtained on P7, P8, P10, P12, P14, P17, P21, & P24 for histopathological studies and RT–PCR analysis. TUNEL was performed to compare the apoptotic response in the neovascular tufts from oxygen–exposed TNFR– (n=8) and B6 mice (n=6). Immunohistochemical analysis of activated Müller cells (GFAP) and microglial cells (F4/80) was done to compare the glial cell response between TNFR– and B6 mice. RT–PCR was used to examine retinal expression of the TNF–α modulated chemokine stromal–derived factor–1 alpha (SDF–1α). Results: TUNEL analysis revealed an increased number of apoptotic cells (∼50%) located in the neovascular tufts of B6 mice as compared to TNFR– mice on P17O2. However, on P21O2 the more extensive tufts observed in TNFR– mice now exhibited increased apoptosis (∼50%) as compared to B6 mice. GFAP immunostaining revealed an intense Müller cell staining pattern in B6 and TNFR– mice on P17O2. GFAP expression remained intense in the TNFR– mice on P21O2 and P24O2 in contrast to reduced expression in the B6 mice. Activated microglial cells were localized to areas of NV in both TNFR– and B6 mice on P17O2 and P21O2. This pattern of microglial localization persisted through P24O2 in the TNFR– mice. Retinal SDF–1α mRNA expression was detected but was not altered in the oxygen–exposed TNFR– or B6 mice at all time points. Conclusions: The absence of functional TNF–α receptors delays the apoptotic response in the neovascular tufts. TNFR– mice also exhibit a prolonged glial response to ischemic–induced injury. Unaltered SDF–1α expression suggests a homeostatic role for this chemokine in the retina. These data suggest that the TNF–α apoptotic pathway may serve as a potential target to reduce retinal NV.

Keywords: retinal neovascularization • apoptosis/cell death • cytokines/chemokines 
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