Abstract
Purpose: :
The vascular primary vitreous undergoes regression of the hyaloid vasculature during the second trimester of gestation. Using proteomic analyses of individual vitreous samples (vitreomics), the human vitreous protein profile was determined at various times during the 4th and 5th months of gestation.
Methods: :
12 eyes from human embryos aged 14 to 20 weeks of gestation were dissected in the fresh state and vitreous samples were immediately frozen at -80 C. Proteomic analysis was performed in each individual vitreous sample with one-dimensional SDS-PAGE and nano-LC tandem mass spectrometry. Results were compared between early 2nd trimester (week 14 to 17.5, N=4), and late 2nd trimester (week 18.5 to 20, N=8) using Student's T-test.
Results: :
There were statistically significant decreases in one protein and increases in the concentrations of 6 protein precursors. Profilin-1 decreased 2.1 fold (P=0.02). Cadherin-2 increased 2.7-fold (P=0.005), Clusterin increased 1.8-fold (P=0.04), Cystatin-C increased 3.7-fold (P=0.0005), Dystroglycan increased 2.2-fold (P=0.002), Glypican-2 increased 2.9-fold (P=0.01), and Pigment Epithelium-Derived Factor (PEDF) increased 3-fold (P=0.002) when comparing early and late 2nd trimester human vitreous.
Conclusions: :
Concurrent with the period of hyaloid vaessel regression, there was a significant decrease in Profilin-1 (actin binding protein) and an increase in Cadherin (cell adhesion protein), Clusterin (apolipoprotein), Cystatin-C (protease inhibitor), Dystroglycan (cell surface protein), Glypican (cell adhesion), and PEDF (angio-inhibitory) precursors during the second trimester of human embryogenesis. PEDF and Clusterin are known to have anti-angiogenic properties that could contribute to vessel regression. Profilin-1 is required for capillary morphogenesis (Exp Cell Res 2009;315:2963-73) and it's decline in late 2nd trimester may also contribute to hyaloid vascular regression. Further vitreomic study is needed to determine the potential role of these factors in regression of the fetal hyaloid vasculature and their potential usefulness as novel therapeutics.
Keywords: vitreous • development • proteomics