DISCUSSION

    VEGF is known as an important pro-angiogenesis cytokine, which plays an important regulating role in both physiological and pathological angiogenesis process. Since PEDF was found to be a potent anti-angiogenesis factor , it has been progressively considered significant and was reported to inhibit retinal capillary endothelial cell proliferation and migration induced by VEGF . Many experiments demonstrated that, it was the impaired levels of PEDF and VEGF that may promote pathological angiogenesis. We found that the aque

    Figure 6 Correlation of PEDF and VEGF in aqueous humor

    Figure 7 Correlation of PEDF and VEGF in vitreous

    ous and vitreous VEGF levels in patients with PDR were significantly higher than those of control. The aqueous and vitreous VEGF levels in patients of PDR with NVI were higher than those without PDR. On the contrary, the aqueous and vitreous PEDF levels were much lower than those of the control. The aqueous and vitreous PEDF levels in patients with PDR and NVI were lower than those without PDR. Boehm performed the ELISA and immunoblotting test to detect the aqueous PEDF and VEGF concentrations in diabetic retinopathy patients. Our experiments could support the conclusion that a change in PEDF and VEGF concentrations may relate to the development of retinal neovascularization. Furthermore, we measured the aqueous levels of the two factors in patients with NVI, and found that a further decreae of PEDF and increase of VEGF may be related to NVI.

    In aphakic eyes, the incidence of iris rubeosis after vitrectomy was higher than in phakic eyes . It has been proposed that angiogenic factors released from the ischemic retina may cause retinal and iris neovascularization. We found no significant correlation of PEDF and VEGF levels between the aqueous humor and serum. This suggested that the aqueous concentrations of the two factors may be less likely influenced by systemic conditions. In the control group, the PEDF and VEGF levels in the aqueous humor did not obviously correlate to those in the vitreous. This might support the conclusion that some amount of PEDF and VEGF may be expressed in the anterior and posterior tissues to maintain its homeostasis. In normal eyes, retinal pigment epithelial cells , Müller cells , cilliary epithelial cells can express and secrete PEDF to keep the cornea and vitreous avascular. Vascular endothelial cells in iris stroma express a small amount of VEGF, which contributes to the reparation and reproliferation of vascular endothelial cells. Our results showed a positive correlation of PEDF levels between aqueous humor and vitreous in PDR patients. In the process of PDR, the decrease of aqueous PEDF concentrations may be a result of vitreous changes. The corneal endothelium and ciliary epithelium also have the function of secreting PEDF, which was not found to be lowered in the process of PDR. We also found that in the PDR group without NVI, that the VEGF levels in aqueous humor positively correlated with that in the vitreous, while in the PDR group with NVI, no correlation of VEGF levels was found between the aqueous humor and the vitreous. In the ischemic diabetic retina, abundant VEGF was expressed in optic neuroganglion cells, retinal pigment epithelial cells, and retinal vascular endothelial cells . Previous studies demonstrated that no abnormal VEGF expression was found in the tissue of rubeosis iridis, including the iris pigment epithelial cell, stromal cell, and endothelial cell. A great deal of VEGF expression was found only in neovascular endothelial cells on the surface of the iris . In patients with PDR, the retina with the condition of chronic ischemia secreted VEGF into the vitreous, which simultaneously diffused to the anterior segment. Once NVI developed, the iris neovascular endothelial cells may produce VEGF in a self-secreting fashion. According to previous and our experimental results, the increased aqueous VEGF levels in patients of PDR with NVI may derive from both, vitreous diffusion and iris neovascular endothelial cells secretion. Our findings also demonstrated that in aqueous humor and vitreous samples, PEDF levels and VEGF levels had negative correlations, which implied that both PEDF and VEGF behaved as an antagonists to each other. This hypothesis was supported by previous researches. In vitro , exogenous VEGF reduced the secretion of PEDF by Müller cells . In the experimental research of retinopathy of premature, PEDF was found to be the substrate to matrix metal protease-2 and -9（MMP-2, MMP-9）. Hypoxia and VEGF resulted in degradation of PEDF by upregulating MMP-2, MMP-9 . However, the real mechanism of the interaction of PEDF and VEGF needs further study. In summary, the decrease of intraocular PEDF levels and increase of VEGF levels may play an important role in the development of PDR. In the process of PDR, the variation of the two factors of aqueous concentrations may be most of the part more locally than systematically effected. Unbalanced distribution of PEDF and VEGF in eyes may play a role in the pathogenesis of NVI and retinal neovascularization. Further research is needed to analyze the source of the changes in PEDF and VEGF levels of PDR patients; this could provide theoretical guiderlines for the clinical diagnosis and treatment.

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