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PURPOSE. Vascular endothelial growth factor (VEGF)-A and placental growth factor (PIGF) are members of a large group of homologous peptides identified as the VEGF family. Although VEGF-A is known to act as a potent angiogenic peptide in the retina, the vasoactive function of PIGF in this tissue is less well defined. This study has sought to elucidate the expression patterns and modulatory role of these growth factors during retinal vascular development and hyaloid regression in the neonatal mouse. METHODS. C57BL6J mice were killed at postnatal days (P)1, P3, P5, P7, P9, and P11. The eyes were enucleated and processed for in situ hybridization and immunocytochemistry and the retinas extracted for total protein or RNA. Separate groups of neonatal mice were also injected intraperitoneally daily from P2 through P9 with either VEGF-neutralizing antibody, PIGF-neutralizing antibody, isotype immunoglobulin (Ig)-G, or phosphate-buffered saline (PBS). The mice were then perfused with fluorescein isothiocyanate (FITC)-dextran, and the eyes were subsequently embedded in paraffin wax or flat mounted. RESULTS. Quantitative (real-time) reverse transcription-polymerase chain reaction (RT-PCR) demonstrated similar expression patterns of VEGF-A and PIGF mRNA during neonatal retinal development, although the fluctuation between time periods was greater overall for VEGF-A. The localization of VEGF-A and PIGF in the retina, as revealed by in situ hybridization and immunohistochemistry, was also similar. Neutralization of VEGF-A caused a significant reduction in the hyaloid and retinal vasculature, whereas PIGF antibody treatment caused a marked persistence of the hyaloid without significantly affecting retinal vascular development. CONCLUSIONS. Although having similar expression patterns in the retina, these growth factors appear to have distinct modulatory influences during normal retinal vascular development and hyaloid regression.

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The glycoxidation products Nepsilon-(carboxymethyl)lysine and pentosidine increase in skin collagen with age and at an accelerated rate in diabetes. Their age-adjusted concentrations in skin collagen are correlated with the severity of diabetic complications. To determine the relative roles of increased glycation and/or oxidation in the accelerated formation of glycoxidation products in diabetes, we measured levels of amino acid oxidation products, distinct from glycoxidative modifications of amino acids, as independent indicators of oxidative stress and damage to collagen in aging and diabetes. We show that ortho-tyrosine and methionine sulfoxide are formed in concert with Nepsilon-(carboxymethyl)lysine and pentosidine during glycoxidation of collagen in vitro, and that they also increase with age in human skin collagen. The age-adjusted levels of these oxidized amino acids in collagen was the same in diabetic and nondiabetic subjects, arguing that diabetes per se does not cause an increase in oxidative stress or damage to extracellular matrix proteins. These results provide evidence for an age-dependent increase in oxidative damage to collagen and support previous conclusions that the increase in glycoxidation products in skin collagen in diabetes can be explained by the increase in glycemia alone, without invoking a generalized, diabetes-dependent increase in oxidative stress.

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PURPOSE: To assess the sensitivity and specificity of models predicting myopia onset among ethnically Chinese children. METHODS: Visual acuity, height, weight, biometry (A-scan, keratometry), and refractive error were assessed at baseline and 3 years later using the same equipment and protocol in primary schools in Xiamen (China) and Singapore. A regression model predicting the onset of myopia < -0.75 diopters (D) after 3 years in either eye among Xiamen children was validated with Singapore data. RESULTS: Baseline data were collected from 236 Xiamen children (mean age, 7.82 ± 0.63 years) and from 1979 predominantly Chinese children in Singapore (7.83 ± 0.84 years). Singapore children were significantly taller and heavier, and had more myopia (31.4% vs. 6.36% < -0.75 D in either eye, P < 0.001) and longer mean axial length. Three-year follow-up was available for 80.0% of Xiamen children and 83.1% in Singapore. For Xiamen, the area under the receiver-operator curve (AUC) in a model including ocular biometry, height, weight, and presenting visual acuity was 0.974 (95% confidence interval [CI], 0.945-0.997). In Singapore, the same model achieved sensitivity, specificity, and positive predictive value of 0.844, 0.650, and 0.669, with an AUC of 0.815 (95% CI, 0.791-0.839). CONCLUSIONS: Accuracy in predicting myopia onset based on simple measurements may be sufficient to make targeted early intervention practical in settings such as Singapore with high myopia prevalence. Models based on cohorts with a greater prevalence of high myopia than that in Xiamen could be used to assess accuracy of models predicting more severe forms of myopia.