Essential role of growth hormone in ischemia-induced retinal neovascularization

Science

Volumn 276, Issue 5319, 1997, Pages 1706-1709

  Smith, Lois E H ^a   Kopchick, John J ^b   Chen, Wen ^b   Knapp, Joanne ^b   Kinose, Fumi ^a   Daley, Douglas ^a   Foley, Eliot ^a   Smith, Roy G ^c   Schaeffer, James M ^c  

^a BOSTON CHILDREN S HOSPITAL   (United States)

^b OHIO UNIVERSITY   (United States)

^c MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GROWTH HORMONE; GROWTH HORMONE ANTAGONIST; SEGLITIDE; SOMATOMEDIN C; UNCLASSIFIED DRUG; VASCULOTROPIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; GROWTH HORMONE BLOOD LEVEL; GROWTH HORMONE RELEASE; HYPOXIA; MOUSE; NONHUMAN; PRIORITY JOURNAL; RETINA NEOVASCULARIZATION; RETINOPATHY; TRANSGENIC MOUSE;

ANIMALS; ENDOTHELIAL GROWTH FACTORS; GROWTH HORMONE; HORMONE ANTAGONISTS; INSULIN-LIKE GROWTH FACTOR I; ISCHEMIA; LYMPHOKINES; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; PEPTIDES, CYCLIC; RECOMBINANT PROTEINS; RETINAL NEOVASCULARIZATION; RETINAL VESSELS; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTORS;

ANIMALIA; MUS MUSCULUS;

EID: 0030863133     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.276.5319.1706     Document Type: Article

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30. These studies adhered to the "Association for Research in Vision and Ophthalmology Statement for the Use of Animals in Ophthalmic and Vision Research." Mice were anesthetized with Avertin and killed by intracardiac perfusion of 4% paraformaldehyde in phosphate-buffered saline. The eyes were enucleated and fixed in 4% paraformaldehyde before paraffin embedding. Over 50 serial axial sections (6 μm) were obtained, starting at the optic nerve head. After staining with periodic acid-Schiff reagent and hematoxylin, 10 sections, each 30 μm apart, were evaluated for a span of 300 μm. Eyes with retinal detachment or inflammation (less than 10% of those studied) were excluded. All retinal vascular cell nuclei anterior to the internal limiting membrane were counted in each section in a fully masked protocol. The average number of neovascular cell nuclei per section per eye is the mean of the 10 counted sections. No vascular cell nuclei anterior to the internal limiting membrane were seen in normal unmanipulated animals. The Student's t test was used to compare qualitative data populations with normal distributions and equal variance. Data were analyzed with the Mann-Whitney Rank Sum Test for populations with nonnormal distributions or unequal variance.
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33. -1).
34. Serum IGF-I (after acid-ethanol extraction) from at least nine mice for each condition reported was assayed by use of IGF-I radioimmunoassay (RIA) kits (Nichols Institute Diagnostics, San Juan Capistrano, CA) (12). Mouse GH was measured by a double-antibody RIA procedure (12). GH levels of MK678-treated mice are the means of total serum measurements from at least nine mice obtained from 4 to 6 hours after injection at each condition. All GH and IGF-I errors indicated are standard deviations. Serum levels of GH were increased in GH agonist E117L transgenic mice compared to controls. GH receptor blockage by GH antagonist G119K results in low serum IGF-I levels that serve as a signal for increased production of murine GH (12). Therefore murine GH levels were increased in G119K transgenic mice. G119K mice were 34% smaller than controls at P28 because of the GH antagonist effect.
35. -1 of MK678, serum IGF-I concentration was used as a predictor of change in retinal neovascularization by simple linear regression. The Pearson correlation coefficient, r, was used as a measure of linear association. Standard error of the estimate (SEE) was used to indicate error of the regression line. Two-tailed P values <0.05 were considered to be statistically significant by use of SPSS software (6.1) (SPSS, Chicago, IL).
36. 32P]deoxycytidine 5′-triphosphate (New England Nuclear, Boston, MA). Autoradiographs were analyzed on a PhosphorImager (Molecular Dynamics) and quantified with ImageQuant PhosphorImager (Molecular Dynamics); Fms-like tyrosine kinase (fit) mRNA was undetectable on Northern blot under all conditions.
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50. We thank X. Xu, R. Sullivan, T. Meehan, R. Webb, K. Cheng, T. W. Wu, and S. Satiritz for assistance and D. Senger and K. Claffey for helpful discussions. Supported in part by grants from the V. Kann Rasmussen Foundation and the National Eye Institute (EY08670 to L.E.H.S.) and the Ohio State Eminent Scholars Program, Sensus Corporation, and the Juvenile Diabetes International (195061 to J.J.K.).