Disease relevance of Retinal Neovascularization

• We conclude that VEGFR-1 is critical in maintaining the vasculature of the neonatal retina, and that activation of VEGFR-1 by PlGF-1 is a selective strategy for preventing oxygen-induced retinal ischemia without provoking retinal neovascularization [1].
• Dihydroethidium imaging analyses showed increased superoxide formation in areas of retinal neovascularization associated with relative retinal hypoxia in a mouse model for oxygen-induced retinopathy [2].
• Using the retinopathy of prematurity model, a mouse model of ischemia-induced retinal neovascularization, we have demonstrated more pronounced retinal neovascularization in 17-day-old transgenic mice overexpressing leptin than in age-matched wild-type littermates [3].
• Insulin-like growth factor-1 (IGF-1) plays important roles in the developing and mature retina and in pathological states characterized by retinal neovascularization, such as diabetic retinopathy [4].
• CONCLUSIONS: The present findings suggest that the AT1-R signaling blockade leads to the selective suppression of pathologic, but not physiological, retinal neovascularization through the inhibition of the inflammatory processes related to pathologic neovascularization [5].

High impact information on Retinal Neovascularization

• Importantly, a naturally occurring form of PEX can be detected in vivo in conjunction with alphavbeta3 expression in tumors and during developmental retinal neovascularization [6].
• Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor [7].
• Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor-type integrins inhibits retinal neovascularization [8].
• The amount of inhibitory PEDF produced by retinal cells was positively correlated with oxygen concentrations, suggesting that its loss plays a permissive role in ischemia-driven retinal neovascularization [9].
• Retinal neovascularization was inhibited in these mice in inverse proportion to serum levels of GH and a downstream effector, insulin-like growth factor-I (IGF-I) [10].

Chemical compound and disease context of Retinal Neovascularization

• Hyperoxia-induced retinal neovascularization was observed in wild-type and heterozygous mice but animals that were homozygous null for c-abl did not develop a vasoproliferative retinopathy in response to hyperoxia [11].
• We have investigated the use of antisense phosphorothioate oligodeoxynucleotides against murine VEGF to inhibit retinal neovascularization and VEGF synthesis in a murine model of proliferative retinopathy [12].
• In conclusion, we demonstrate for the first time an in vivo intracellular mechanism for compensation of integrin function and that p53 and alpha(v)-integrins act in concert during retinal neovascularization [13].
• Octreotide combined with emodin or 4,5,6,7-tetrabromobenzotriazole blocked mouse retinal neovascularization more efficiently than either compound alone [14].
• In conclusion, NAD(P)H oxidase activity is required for hypoxia-stimulated increases in VEGF expression and retinal neovascularization [2].

Biological context of Retinal Neovascularization

• Since VEGF is required for iris and retinal neovascularization in animal models of retinal ischemia, we tested whether IGF-I could act as an indirect angiogenic factor by increasing VEGF gene expression [15].
• Eicosapentaenoic acid (EPA), a substrate for DHA, is the parent fatty acid for a family of eicosanoids that have the potential to affect AA-derived eicosanoids implicated in abnormal retinal neovascularization, vascular permeability, and inflammation [16].
• CONCLUSIONS: These results indicate that the maintenance of Tbdn-1 expression is important for retinal blood vessel homeostasis and for controlling retinal neovascularization in adults [17].
• Furthermore, siRNA-mediated inhibition of PRL mRNA increased retinal neovascularization threefold and resulted in a significant increase in vasodilation [18].
• Inhibition of the activity of uPAR suppresses retinal neovascularization, possibly through a reduction in cell-associated proteolytic activity, cell signaling, or cell-matrix adhesion necessary for cell migration during angiogenesis [19].

Anatomical context of Retinal Neovascularization

• Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization [20].
• The PEDF concentrations in patients with PDR (P < 0.001) or extensive nondiabetic retinal neovascularization caused by retinal-vein occlusion (P < 0.001) were lower than in control patients [21].
• EphrinA1 inhibits vascular endothelial growth factor-induced intracellular signaling and suppresses retinal neovascularization and blood-retinal barrier breakdown [22].
• CONCLUSIONS: Vascular endothelial growth factor expression precedes retinal neovascularization in the retinas and the optic nerves of humans with diabetes [23].
• In conclusion, CM from retinal pericytes suppresses PKC-p44/42 MAPK signaling, inhibits endothelial cell growth, and prevents retinal neovascularization [24].

Gene context of Retinal Neovascularization

• These data suggest that c-abl is required for the hyperoxia-induced retinal neovascularization and hyperoxia-induced decrease in VEGF mRNA levels [11].
• This study was designed to test the hypothesis that altered expression of FGF2 in the retina affects the development of retinal neovascularization [25].
• Selective inhibitors of eNOS may be needed for treatment of retinal neovascularization [26].
• Potential role of the angiopoietin/tie2 system in ischemia-induced retinal neovascularization [27].
• RESULTS: The concentration of IL-8 in vitreous fluid of patients with retinal neovascularization was significantly higher than that of patients without neovascular disease [28].

Analytical, diagnostic and therapeutic context of Retinal Neovascularization

• We developed a novel mouse xenotransplantation model of retinal neovascularization to test human hematopoietic cell plasticity [29].
• PEDF expression is suppressed by hypoxia, and changes in PEDF have been correlated to the development of retinal neovascularization in animal models of hypoxic eye disease [21].
• After treatment with doxycycline to induce Ang2 expression, intravitreous injection of AGV.VEGF caused retinal neovascularization in addition to corneal and iris neovascularization [30].
• PURPOSE: To report a case of macular ischemia and retinal neovascularization in a patient who received cisplatin related chemotherapy [31].
• RESULTS: Successful regression of retinal neovascularization was achieved after argon green laser panretinal photocoagulation in addition to oral steroid and salazopyrine [32].

References