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The relationship of retinal VEGF and retinal IGF-1 mRNA with neovascularization in an acidosis-induced model of retinopathy of prematurity.
Curr Eye Res. 2006 Feb; 31(2):163-9.CE

Abstract

PURPOSE

Acidosis-induced retinopathy (AIR) in the neonatal rat provides an alternative model for retinopathy of prematurity (ROP). We studied the relationship of vascular endothelial growth factor (VEGF) retinal mRNA and insulin-like growth factor-1 (IGF-1) retinal mRNA expression with the emergence of neovascularization (NV) in AIR.

METHODS

Two hundred seventy-five newborn Sprague-Dawley rats were raised in 11 expanded litters of 25. Using our established AIR model, acidosis was induced by twice-daily gavage with NH4Cl from day 2 to day 8 of life (n=175). Rats were sacrificed at days 5, 8, and 10. Nongavaged rats were used as age-matched controls (n=100). Retinae from left eyes were dissected, flatmounts were ADPase-stained, and the presence and severity of NV was scored in a masked manner. Individual right retinae were processed for analysis of retinal VEGF and IGF-1 mRNA using quantitative real-time reverse-transcriptase PCR (qRT-PCR).

RESULTS

Retinal VEGF mRNA was increased 1.4-fold at day 10 in AIR, when compared with age-matched controls (p=0.03). This correlated with maximal NV at day 10 in AIR. Retinal IGF-1 mRNA was decreased to 82% of its normal expression on day 8 (p=0.006), prior to maximal NV, before returning to normal expression at day 10, when compared with nonacidotic controls.

CONCLUSIONS

In AIR, preretinal neovascularization is associated with decreased retinal IGF-1 mRNA prior to maximal NV and increased retinal VEGF mRNA at the time of maximal NV. These growth factor changes in AIR are similar to those seen with hypercarbic oxygen-induced retinopathy. The retinal IGF-1 pathway may provide an alternative target for therapeutic intervention in abnormal retinal angiogenesis.

Authors+Show Affiliations

Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, Minnesota 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, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16500767

Citation

Leske, David A., et al. "The Relationship of Retinal VEGF and Retinal IGF-1 mRNA With Neovascularization in an Acidosis-induced Model of Retinopathy of Prematurity." Current Eye Research, vol. 31, no. 2, 2006, pp. 163-9.
Leske DA, Wu J, Mookadam M, et al. The relationship of retinal VEGF and retinal IGF-1 mRNA with neovascularization in an acidosis-induced model of retinopathy of prematurity. Curr Eye Res. 2006;31(2):163-9.
Leske, D. A., Wu, J., Mookadam, M., Chen, Y., Fautsch, M. P., Holmes, J. M., & Lanier, W. L. (2006). The relationship of retinal VEGF and retinal IGF-1 mRNA with neovascularization in an acidosis-induced model of retinopathy of prematurity. Current Eye Research, 31(2), 163-9.
Leske DA, et al. The Relationship of Retinal VEGF and Retinal IGF-1 mRNA With Neovascularization in an Acidosis-induced Model of Retinopathy of Prematurity. Curr Eye Res. 2006;31(2):163-9. PubMed PMID: 16500767.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The relationship of retinal VEGF and retinal IGF-1 mRNA with neovascularization in an acidosis-induced model of retinopathy of prematurity. AU - Leske,David A, AU - Wu,Jianmin, AU - Mookadam,Martina, AU - Chen,Yi, AU - Fautsch,Michael P, AU - Holmes,Jonathan M, AU - Lanier,William L, PY - 2006/2/28/pubmed PY - 2006/4/19/medline PY - 2006/2/28/entrez SP - 163 EP - 9 JF - Current eye research JO - Curr Eye Res VL - 31 IS - 2 N2 - PURPOSE: Acidosis-induced retinopathy (AIR) in the neonatal rat provides an alternative model for retinopathy of prematurity (ROP). We studied the relationship of vascular endothelial growth factor (VEGF) retinal mRNA and insulin-like growth factor-1 (IGF-1) retinal mRNA expression with the emergence of neovascularization (NV) in AIR. METHODS: Two hundred seventy-five newborn Sprague-Dawley rats were raised in 11 expanded litters of 25. Using our established AIR model, acidosis was induced by twice-daily gavage with NH4Cl from day 2 to day 8 of life (n=175). Rats were sacrificed at days 5, 8, and 10. Nongavaged rats were used as age-matched controls (n=100). Retinae from left eyes were dissected, flatmounts were ADPase-stained, and the presence and severity of NV was scored in a masked manner. Individual right retinae were processed for analysis of retinal VEGF and IGF-1 mRNA using quantitative real-time reverse-transcriptase PCR (qRT-PCR). RESULTS: Retinal VEGF mRNA was increased 1.4-fold at day 10 in AIR, when compared with age-matched controls (p=0.03). This correlated with maximal NV at day 10 in AIR. Retinal IGF-1 mRNA was decreased to 82% of its normal expression on day 8 (p=0.006), prior to maximal NV, before returning to normal expression at day 10, when compared with nonacidotic controls. CONCLUSIONS: In AIR, preretinal neovascularization is associated with decreased retinal IGF-1 mRNA prior to maximal NV and increased retinal VEGF mRNA at the time of maximal NV. These growth factor changes in AIR are similar to those seen with hypercarbic oxygen-induced retinopathy. The retinal IGF-1 pathway may provide an alternative target for therapeutic intervention in abnormal retinal angiogenesis. SN - 0271-3683 UR - https://www.unboundmedicine.com/medline/citation/16500767/The_relationship_of_retinal_VEGF_and_retinal_IGF_1_mRNA_with_neovascularization_in_an_acidosis_induced_model_of_retinopathy_of_prematurity_ DB - PRIME DP - Unbound Medicine ER -