Increased expression of angiogenic growth factors in age-related maculopathy

Kliffen, Mike; Sharma, Hari Shanker; Mooy, Cornelia M.; Kerkvliet, S.; Jong, P.T.V.M. de

doi:10.1136/bjo.81.2.154

Cited by 455 publications

(316 citation statements)

References 41 publications

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“…VEGF is a potent endothelial cell mitogen and angiogenic growth factor strongly expressed in postmortem AMD eyes both with and without choroidal neovascularization [Lip et al, 2001]. Over-expression of VEGF in the RPE, even if only temporarily, is sufficient to induce choroidal neovascularization in the rat eye [Kliffen et al, 1997;Spilsbury et al, 2000]. CCL2 also has been associated with further deterioration and degeneration, especially in advanced disease stages [Ambati et al, 2003].…”

Section: Discussionmentioning

confidence: 99%

An apolipoprotein E variant may protect against age‐related macular degeneration through cytokine regulation

Bojanowski

Shen

Chew

et al. 2006

Environ and Mol Mutagen

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Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness among the elderly in Western countries. Genetic factors, age, cigarette smoking, nutrition, and exposure to light have been identified as AMD risk factors. In this study, we investigated the association between ApoE C112R/R158C single nucleotide polymorphisms (which determine the E2, E3, and E4 isoforms) and age-related macular degeneration (AMD), and the mechanism underlying the association. Genomic DNA was extracted from 133 clinically screened controls, 94 volunteers with a younger mean age, 120 patients with advanced AMD, and 40 archived ocular AMD slides for single nucleotide polymorphism typing. The effects of recombinant ApoE isoforms on CCL2 (a chemokine), CX3CR1 (a chemokine receptor), and VEGF (a cytokine) expression in cultured human retinal pigment epithelium (RPE) cells were tested and serum cholesterol profiles of the clinically screened subjects were analyzed. ApoE112R (E4) distribution differed significantly between AMD patients and controls. ApoE112R allele frequency was 10.9% in the AMD group when compared with 16.5% in the younger controls and 18.8% in the clinically screened controls. The pathologically diagnosed archived AMD cases had the lowest allele frequency of 5%. No significant differences in ApoE158C (E2) distribution were observed among the groups. A meta-analysis of 8 cohorts including 4,289 subjects showed a strong association between AMD and 112R, but not 158C. In vitro studies found that recombinant ApoE suppresses CCL2 and VEGF expression in RPE cells. However, the E4 isoform showed more suppression than E3 in both cases. These results further confirm the association between ApoE112R and a decreased risk of AMD development. The underlying mechanisms may involve differential regulation of both CCL2 and VEGF by the ApoE isoforms.

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Section: Discussionmentioning

confidence: 99%

An apolipoprotein E variant may protect against age‐related macular degeneration through cytokine regulation

Bojanowski

Shen

Chew

et al. 2006

Environ and Mol Mutagen

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“…28,36 It is widely believed that VEGF up-regulation also plays a major part in the development of ocular NV. [6][7][8][9][20][21][22] Several studies have further shown that inhibition of VEGF activity by administration of VEGF-specific kinase inhibitors, VEGF antibodies, VEGF receptors and VEGF antisense oligonucleotides successfully suppressed the development of retinal and choroidal NV. [37][38][39][40] In particular, Honda et al 41 showed that expression of adenovirus-mediated sFlt-1 suppressed choroidal NV.…”

Section: Discussionmentioning

confidence: 99%

“…The cornea and iris were separated into flat mounts and examined under fluorescence microscopy (BX60; Olympus, Japan). The flat mounts were further embedded in optical cutting temperature compound (Sakara Finetek, Torrance, CA, USA), frozen and sectioned at [8][9][10][11][12] m. Real-time monitoring of GFP expression following subretinal injection was achieved by fluorescence fundus photography. 16 The percentage GFPpositive area within the injection area was determined from the fluorescence fundus photograph using image analysis software based on the Matrox Imaging Library (Canada).…”

Section: Fluorescence Microscopy and Fluorescence Fundus Photographymentioning

confidence: 99%

“…The up-regulation of VEGF and its receptors in human neovascular ocular tissues has been well documented. [6][7][8][9][10][11] Several studies have further shown that overexpression of VEGF in the retina by adenoviral vectors or in transgenic animal models resulted in retinal and choroidal NV. [12][13][14] Current conventional treatments of retinal and choroidal NV such as laser photocoagulation and surgical intervention provide only symptomatic treatment of the disease without addressing the underlying cause.…”

Section: Introductionmentioning

confidence: 99%

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Potential long-term inhibition of ocular neovascularisation by recombinant adeno-associated virus-mediated secretion gene therapy

et al. 2002

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“…[11][12][13][14] In surgically removed CNV, an inflammatory reaction including macrophages and foreign body giant cells has been observed that may stimulate CNV growth. 15,16 Radiotherapy was suggested as a promising, noninvasive treatment option.…”

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confidence: 99%

Results of radiotherapy of subfoveal neovascularization with 16 and 20 Gy

Hoeller

Fuisting

Schwartz

et al. 2004

Eye

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Purpose In a nonrandomized, prospective study the efficacy of radiotherapy with 16 and 20 Gray (Gy) for subfoveal neovascularization in age-related macular degeneration (ARMD) was analysed. Material and Methods From 1996 to 1998, 63 eyes were irradiated with 16 Gy and 38 eyes with 20 Gy for exudative ARMD. A total of 12 eyes had classic ARMD, 89 eyes occult ARMD, median baseline visual acuity (VA) was 6/30 (range: 3/60-6/9.5), median age was 78 years. Risk factors (type of ARMD, baseline VA) were evenly distributed in both groups. Median follow-up was 1.3 years (range: 4 months-4.7 years). VA of 71 line or better and unchanged size and activity of the membrane in fluorescein angiography were defined as stable. Actuarial methods were used. Results Median loss of VA was À3 lines (range: À14 to þ 5), neovascularization remained unchanged or decreased in size and activity in 35 eyes. At 18 months, the probability of stabilized VA was 0.4 (95% confidence interval (CI): 0.3-0.5), at 24 months 0.3 (95% CI: 0.2-0.4). Radiation dose, type of ARMD or baseline VA had no significant impact on outcome of VA and membrane size and activity (P40.05). Side effects were mild and transient increased tearing. Conclusion In this study, the results after radiotherapy were comparable to the natural course of the disease. An impact of radiation dose (16 vs 20 Gy) on stabilizing visual acuity and subfoveal neovascularization could not be shown. The results of studies on dose escalation using very small fields and high radiation doses should be awaited.

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Increased expression of angiogenic growth factors in age-related maculopathy

Cited by 455 publications

References 41 publications

An apolipoprotein E variant may protect against age‐related macular degeneration through cytokine regulation

An apolipoprotein E variant may protect against age‐related macular degeneration through cytokine regulation

Potential long-term inhibition of ocular neovascularisation by recombinant adeno-associated virus-mediated secretion gene therapy

Results of radiotherapy of subfoveal neovascularization with 16 and 20 Gy

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