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The role of VEGF and IGF-1 in a hypercarbic oxygen-induced retinopathy rat model of ROP.
Mol Vis. 2004 Jan 21; 10:43-50.MV

Abstract

PURPOSE

We have previously described a severe form of oxygen-induced retinopathy (OIR) in the neonatal rat, analogous to human retinopathy of prematurity (ROP), where carbon dioxide is added to the inspired environment (hypercarbic OIR). We studied the time course of emergence and resolution of neovascularization (NV) in normocarbic OIR and hypercarbic OIR and the associated changes in VEGF and IGF-1 mRNA levels in hypercarbic OIR.

METHODS

550 newborn Sprague-Dawley rats were raised in 22 expanded litters of 25. Beginning at day 1 of life, rats were exposed to 7 daily cycles of hyperoxia (80% O2, 20.5 h) and hypoxia (10% O2, 0.5 h) with a gradual return to 80% O2 over 3 h. Inspired CO2 was maintained at 0.2% for 200 rats (normocarbic OIR) and 10% for 100 rats (hypercarbic OIR). Rats were sacrificed after a subsequent 5 day room air recovery period. An additional 250 rats raised in room air served as age matched controls. Retinae from left eyes were dissected and flatmounts were ADPase-stained. The presence and severity of NV was scored in a masked manner. Right eyes in hypercarbic OIR litters and room air controls were processed for analysis of VEGF and IGF-1 mRNA.

RESULTS

In normocarbic OIR, NV started to emerge before room air recovery began at day 8. It was maximal at day 10 and resolved by day 20. In hypercarbic OIR, a similar pattern was seen, with emergence prior to day 8, peak at day 13 and resolution by day 20. In hypercarbic OIR, retinal VEGF mRNA was decreased at day 8 and increased at day 10 compared to room air controls, correlating with maximal NV. Retinal IGF-1 mRNA was not increased at any time in hypercarbic OIR compared to room air controls.

CONCLUSIONS

Neovascularization resulting from normocarbic OIR or hypercarbic OIR occurs before room air recovery. Retinal VEGF mRNA was downregulated and subsequently upregulated prior to maximal NV in hypercarbic OIR. Neovascularization in the hypercarbic OIR model does not appear to be associated with increased retinal IGF-1 mRNA.

Authors+Show Affiliations

Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14758338

Citation

Leske, David A., et al. "The Role of VEGF and IGF-1 in a Hypercarbic Oxygen-induced Retinopathy Rat Model of ROP." Molecular Vision, vol. 10, 2004, pp. 43-50.
Leske DA, Wu J, Fautsch MP, et al. The role of VEGF and IGF-1 in a hypercarbic oxygen-induced retinopathy rat model of ROP. Mol Vis. 2004;10:43-50.
Leske, D. A., Wu, J., Fautsch, M. P., Karger, R. A., Berdahl, J. P., Lanier, W. L., & Holmes, J. M. (2004). The role of VEGF and IGF-1 in a hypercarbic oxygen-induced retinopathy rat model of ROP. Molecular Vision, 10, 43-50.
Leske DA, et al. The Role of VEGF and IGF-1 in a Hypercarbic Oxygen-induced Retinopathy Rat Model of ROP. Mol Vis. 2004 Jan 21;10:43-50. PubMed PMID: 14758338.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of VEGF and IGF-1 in a hypercarbic oxygen-induced retinopathy rat model of ROP. AU - Leske,David A, AU - Wu,Jianmin, AU - Fautsch,Michael P, AU - Karger,Randy A, AU - Berdahl,John P, AU - Lanier,William L, AU - Holmes,Jonathan M, Y1 - 2004/01/21/ PY - 2004/2/6/pubmed PY - 2004/2/18/medline PY - 2004/2/6/entrez SP - 43 EP - 50 JF - Molecular vision JO - Mol Vis VL - 10 N2 - PURPOSE: We have previously described a severe form of oxygen-induced retinopathy (OIR) in the neonatal rat, analogous to human retinopathy of prematurity (ROP), where carbon dioxide is added to the inspired environment (hypercarbic OIR). We studied the time course of emergence and resolution of neovascularization (NV) in normocarbic OIR and hypercarbic OIR and the associated changes in VEGF and IGF-1 mRNA levels in hypercarbic OIR. METHODS: 550 newborn Sprague-Dawley rats were raised in 22 expanded litters of 25. Beginning at day 1 of life, rats were exposed to 7 daily cycles of hyperoxia (80% O2, 20.5 h) and hypoxia (10% O2, 0.5 h) with a gradual return to 80% O2 over 3 h. Inspired CO2 was maintained at 0.2% for 200 rats (normocarbic OIR) and 10% for 100 rats (hypercarbic OIR). Rats were sacrificed after a subsequent 5 day room air recovery period. An additional 250 rats raised in room air served as age matched controls. Retinae from left eyes were dissected and flatmounts were ADPase-stained. The presence and severity of NV was scored in a masked manner. Right eyes in hypercarbic OIR litters and room air controls were processed for analysis of VEGF and IGF-1 mRNA. RESULTS: In normocarbic OIR, NV started to emerge before room air recovery began at day 8. It was maximal at day 10 and resolved by day 20. In hypercarbic OIR, a similar pattern was seen, with emergence prior to day 8, peak at day 13 and resolution by day 20. In hypercarbic OIR, retinal VEGF mRNA was decreased at day 8 and increased at day 10 compared to room air controls, correlating with maximal NV. Retinal IGF-1 mRNA was not increased at any time in hypercarbic OIR compared to room air controls. CONCLUSIONS: Neovascularization resulting from normocarbic OIR or hypercarbic OIR occurs before room air recovery. Retinal VEGF mRNA was downregulated and subsequently upregulated prior to maximal NV in hypercarbic OIR. Neovascularization in the hypercarbic OIR model does not appear to be associated with increased retinal IGF-1 mRNA. SN - 1090-0535 UR - https://www.unboundmedicine.com/medline/citation/14758338/The_role_of_VEGF_and_IGF_1_in_a_hypercarbic_oxygen_induced_retinopathy_rat_model_of_ROP_ DB - PRIME DP - Unbound Medicine ER -