Differences in the temporal expression of regulatory growth factors during choroidal neovascular development

Hu, Wenzheng; Criswell, Mark H.; Fong, Shao-Ling; Temm, Constance J.; Gangaraju, Rajashekhar; Cornell, T.L.; Clauss, Matthias

doi:10.1016/j.exer.2008.10.014

Cited by 40 publications

(36 citation statements)

References 78 publications

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“…Of the three factors studied, VEGF was the last to be upregulated, implying a less significant role in early CNV development. 45 An increase in VEGF expression was observed in C3-injected eyes 3 days after injection but could not be attributed to C3 expression because a similar increase was observed in GFP-injected eyes. This increase in VEGF expression was not detectable in C3-injected retinas at the 8-day time point.…”

Section: Discussionmentioning

confidence: 79%

Expression of Complement Component 3 (C3) from an Adenovirus Leads to Pathology in the Murine Retina

Cashman

Desai

Ramo

et al. 2011

Invest. Ophthalmol. Vis. Sci.

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Section: Discussionmentioning

confidence: 79%

Expression of Complement Component 3 (C3) from an Adenovirus Leads to Pathology in the Murine Retina

Cashman

Desai

Ramo

et al. 2011

Invest. Ophthalmol. Vis. Sci.

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“…Stahl et al [26] reported that combined inhibition of VEGF and FGF-2 was a superior therapy compared to single inhibition of VEGF in the treatment of CNV. Hu et al [27] found that the mRNA and protein level of FGF-2 in the RPE and RPE/choroidal tissues increased quickly within hours after a laser treatment. By 3 days after laser treatment, the increased expression of VEGF protein could be measured, and the expression of FGF-2 reached a peak.…”

Section: Discussionmentioning

confidence: 99%

“…VEGF expression peaked at 7 days after laser treatment. Hu et al [27] concluded that FGF-2 was important as an initial regulator of neovascularisation, and VEGF may be important during later phases of angiogenesis. In some neurological disorders, it was reported that microglia was one source of FGF-2 [46,47] .…”

Section: Discussionmentioning

confidence: 99%

“…Apart from VEGF, other pro-angiogenic factors like PDGF-β [17,24,25] , FGF [26][27][28][29] , TGF-β [17,[29][30][31][32] , and IL-8 [33][34][35][36] were also reported to be involved in the pathological process of AMD. Zehetner et al [24] compared the plasma levels of PDGF-β in neovascular AMD patients with healthy controls and found that there was a significantly higher plasma PDGF-β level in neovascular AMD patients than in healthy controls.…”

Section: Discussionmentioning

confidence: 99%

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Behaviour of CD11b-Positive Cells in an Animal Model of Laser-Induced Choroidal Neovascularisation

Heiduschka

Alex

et al. 2017

Ophthalmologica

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Background/Aim: Immune cells, e.g. microglial cells of the retina, appear to be involved in pathological processes in neovascular age-related macular degeneration. Therefore, the purpose of this study was to immunohistochemically check the expression of various factors and cytokines by CD11b-positive (CD11b+) immune cells in an animal model of choroidal neovascularisation (CNV). Methods: We used the animal model of laser-induced CNV in mice. Eyes were isolated at 1, 4, 7, and 14 days after laser treatment. Cryosections were prepared and checked immunohistochemically for the presence of different growth factors and cytokines on microglial cells and other immune cells identified by CD11b immunoreactivity. Results: We found that the number of CD11b+ cells at the laser spots increased dramatically 4 days after laser treatment, the majority of them entering the laser spot most probably by migration. CD11b+ cells in the laser spot were positive for a variety of pro-angiogenic factors, such as PDGF-β, FGF-1, FGF-2, and TGF-β₁. They were also positive for some inflammatory cytokines, in particular TNF-α, IL-6, and CXCL1. In non-treated retinas, CD11b+ cells showed almost no immunoreactivity for these proteins. Conclusion: Microglial cells, macrophages, and other CD11b+ cells may promote the neovascularisation in the laser spot and show a moderate inflammatory behaviour. Immunoreactivity for most of these molecules was found to decrease during the time of observation. Modulation of immune cell activity may thus be a tool to reduce the extent of CNV.

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“…To inhibit tumour growth, a combination of three anti-HGF mAbs may be necessary, which may imply that multiple HGF epitopes should be targeted for cytokine inhibition, a difficult approach for drug development 56. Hu et al showed in the laser-induced CNV model that there was a 25% increase in VEGF expression which remained at a low-level plateau and that the neovascularisation corresponded to HGF and FGF expansion into the CNV 57. These molecular and immunocytochemical results suggest that FGF and HGF may be important as initial regulators of neovascularisation in the CNV model.…”

Section: Hepatocyte Growth Factormentioning

confidence: 99%

Cytokines in neovascular age-related macular degeneration: fundamentals of targeted combination therapy

Dias¹,

Rodrigues

Maia

et al. 2011

British Journal of Ophthalmology

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The neovascular form of age-related macular degeneration (AMD), called wet-AMD or choroidal neovascularisation, begins with damage to the outer retinal cells and retinal pigment epithelium (RPE), which elicits a cascade of inflammatory and angiogenic responses leading to neovascularisation under the macula. Studies showed that oxidative damage, chronic inflammation of the RPE and complement misregulation work at different steps of this disease. After established neovascularisation, several pro- and antiangiogenic agents start to play an important role. Vascular endothelial growth factors (VEGFs) are the most specific and potent regulators of angiogenesis, which are inhibited by intravitreal injections of ranibizumab, bevacizumab, VEGF Trap, pegaptanib sodium and other agents under investigation. Pigment epithelium-derived factor, on the other hand, shows neuroprotective and antiangiogenic activities. Hepatocyte growth factor (HGF) has a mitogenic effect on a wide range of epithelial and endothelial cells, and it is inhibited by an anti-HGF monoclonal antibody. Platelet-derived growth factor is a potent chemoattractant and mitogen for both fibroblasts and retinal RPE cells, which has been inhibited experimentally by VEGF Trap and human anti-platelet-derived growth factor-D monoclonal antibody. Fibroblast growth factor-2 has pleiotropic effects in different cell and organ systems, and it is blocked by anti-FGF antibodies, with a greater benefit regarding antiangiogenesis when combined treatment with anti-VEGF is performed. Tumour necrosis factor alpha is expressed in the retina and the choroid, and its blockade in choroidal neovascularisation includes the use of monoclonals such as infliximab. This paper reviews the most important cytokines involved in the pathogenesis of wet-AMD, with emphasis on potential combined therapies for disease control.

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Differences in the temporal expression of regulatory growth factors during choroidal neovascular development

Cited by 40 publications

References 78 publications

Expression of Complement Component 3 (C3) from an Adenovirus Leads to Pathology in the Murine Retina

Expression of Complement Component 3 (C3) from an Adenovirus Leads to Pathology in the Murine Retina

Behaviour of CD11b-Positive Cells in an Animal Model of Laser-Induced Choroidal Neovascularisation

Cytokines in neovascular age-related macular degeneration: fundamentals of targeted combination therapy

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