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
AU - Wu, Jianmin
AU - Mookadam, Martina
AU - Chen, Yi
AU - Fautsch, Michael
AU - Holmes, Jonathan
AU - Lanier, William
N1 - Funding Information:
Supported by National Institutes of Health Grant EY12798 (J.M.H.), Research to Prevent Blindness, Inc., New York, New York. (J.M.H. as RPB Olga Keith Weiss Scholar and an unrestricted grant to the Department of Ophthalmology, Mayo Clinic), Mayo Foundation, Rochester, Minnesota, and the philanthropy of Margaret Schroeder (J.M.H.).
PY - 2006/2
Y1 - 2006/2
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 NH 4 Cl 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.
AB - 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 NH 4 Cl 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.
KW - Acidosis
KW - Insulin-like growth factor
KW - Retinal neovascularization
KW - Retinopathy of prematurity
KW - Vascular endothelial growth factor
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U2 - 10.1080/02713680500507281
DO - 10.1080/02713680500507281
M3 - Article
C2 - 16500767
AN - SCOPUS:33644614300
SN - 0271-3683
VL - 31
SP - 163
EP - 169
JO - Current Eye Research
JF - Current Eye Research
IS - 2
ER -