Age-Related Macular Degeneration

Gottlieb, Justin L.

doi:10.1001/jama.288.18.2233

Cited by 62 publications

(38 citation statements)

References 23 publications

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“…Relative to what is found in light-skinned individuals of mixed European descent, exudative AMD is 55% less frequent in African-Americans and 46% less frequent in Asian-Americans. These findings support the hypothesis that lower pigmentation is a risk factor for neovascular AMD (1)(2)(3). Studies examining the correlation between race, ethnicity, and incidence of uveal melanoma indicate an influence of iris color on the disease.…”

Section: Introductionsupporting

confidence: 80%

Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment

Adini¹,

Ghosh²,

Adini³

et al. 2013

J. Clin. Invest.

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Studies have established that pigmentation can provide strong, protective effects against certain human diseases. For example, angiogenesis-dependent diseases such as wet age-related macular degeneration and infantile hemangioma are more common in light-skinned individuals of mixed European descent than in AfricanAmericans. Here we found that melanocytes from light-skinned humans and albino mice secrete high levels of fibromodulin (FMOD), which we determined to be a potent angiogenic factor. FMOD treatment stimulated angiogenesis in numerous in vivo systems, including laser-induced choroidal neovascularization, growth factor-induced corneal neovascularization, wound healing, and Matrigel plug assays. Additionally, FMOD enhanced vascular sprouting during normal retinal development. Deletion of Fmod in albino mice resulted in a marked reduction in the amount of neovascularization induced by retinal vein occlusion, corneal growth factor pellets, and Matrigel plugs. Our data implicate the melanocyte-secreted factor FMOD as a key regulator of angiogenesis and suggest an underlying mechanism for epidemiological differences between light-skinned individuals of mixed European descent and African-Americans. Furthermore, inhibition of FMOD in humans has potential as a therapeutic strategy for treating angiogenesis-dependent diseases. Relative to what is found in light-skinned individuals of mixed European descent, exudative AMD is 55% less frequent in African-Americans and 46% less frequent in Asian-Americans. These findings support the hypothesis that lower pigmentation is a risk factor for neovascular AMD (1-3). Studies examining the correlation between race, ethnicity, and incidence of uveal melanoma indicate an influence of iris color on the disease. The frequency of uveal melanoma is highest in light-skinned individuals of mixed European descent, followed by Hispanics, Asians, and African-Americans, with an 18:1 ratio of incidence between light-skinned individuals of mixed European descent and African-Americans (4-6). Similar to the trend of occurrence seen with wet AMD, cutaneous melanoma and infantile hemangioma are much more prevalent in light-skinned individuals of mixed European descent than AfricanAmericans. These facts suggest that low levels of melanin correlate with the development of angiogenic ocular and skin diseases. Since intracellular pigment levels of retinal pigment epithelium (RPE) cells do not differ greatly among races, our studies focused on melanocytes, the main source of ocular pigment.

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Section: Introductionsupporting

confidence: 80%

Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment

Adini¹,

Ghosh²,

Adini³

et al. 2013

J. Clin. Invest.

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“…Age-related macular degeneration (AMD) is a chronic, progressive disease that remains the leading cause of blindness in Americans over the age of 55 years [14]. The majority of vision loss is due to neovascular AMD, the advanced form of the disease where immature vessels grow from the choroid into the subretinal space [12].…”

Section: Introductionmentioning

confidence: 99%

Identification of Chlamydia pneumoniae within human choroidal neovascular membranes secondary to age-related macular degeneration

Kalayoglu

Bula

Arroyo

et al. 2005

Graefe's Arch Clin Exp Ophthalmo

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Age-related macular degeneration (AMD) is a leading cause of blindness in the United States, and increasing evidence suggests that it is an inflammatory disease. The prokaryotic obligate intracellular pathogen Chlamydia pneumoniae is emerging as a novel risk factor in cardiovascular disease, and recent sero-epidemiological data suggest that C. pneumoniae infection is also associated with AMD. In this study, we examined choroidal neovascular membrane (CNV) tissue from patients with neovascular AMD for the presence of C. pneumoniae and determined whether the pathogen can dysregulate the function of key cell types in ways that can cause neovascular AMD. Nine CNV removed from patients with neovascular AMD were examined for the presence of C. pneumoniae by immunohistochemistry (IHC) and polymerase chain reaction (PCR); in addition, we performed PCR on nine non-AMD eyes, and IHC on five non-AMD CNV, seven non-AMD eyes, and one internal limiting membrane specimen. Finally, human monocyte-derived macrophages and retinal pigment epithelial (RPE) cells were exposed to C. pneumoniae and assayed in vitro for the production of pro-angiogenic immunomodulators (VEGF, IL-8, and MCP-1). C. pneumoniae was detected in four of nine AMD CNV by IHC and two of nine AMD CNV by PCR, induced VEGF production by human macrophages, and increased production of IL-8 and MCP-1 by RPE cells. In contrast, none of the 22 non-AMD specimens showed evidence for C. pneumoniae. These data indicate that a pathogen capable of inducing chronic inflammation and pro-angiogenic cytokines can be detected in some AMD CNV, and suggest that infection may contribute to the pathogenesis of AMD.

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“…In contrast, for the vast majority of CNV, which are subfoveal, laser photocoagulation gives little benefit due to the deleterious effect on the overlying sensory retina, resulting in visual deterioration immediately after treatment, and only a small longterm benefit in comparison with the natural course of the disease, as well as a high recurrence rate (Macular Photocoagulation Study Group 1991a, 1991b, 1993. Less than 10% of CNV in AMD are eligible for laser photocoagulation due to subfoveal localization, overly large areas of leakage or poor alignment, and as many as 66% may recur afterwards (Macular Photocoagulation Study Group 1991a;Gottlieb 2002).…”

Section: Introductionmentioning

confidence: 99%

Transpupillary thermotherapy for occult subfoveal choroidal neovascularization: a 1‐year, prospective randomized pilot study

Gustavsson

Agardh

2005

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: To evaluate the 1-year effect of transpupillary thermotherapy (TTT) on occult choroidal neovascularization membranes (CNV). Methods: In this prospective, randomized, controlled pilot study of 28 patients with occult or minimally classic (< 10%) neovascularization membranes with a diameter less than 4500 mm, 19 patients were treated with TTT, while nine received sham treatment. Outcome measures were membrane diameter, visual acuity and reading ability. Results: The median age of patients randomized to TTT was 78 years (range 24 years); that of patients randomized to sham was 79 years (range 9 years). There was no difference regarding membrane diameter at baseline between the two groups; the median membrane diameters were 3400 mm (range 2400 mm) in the TTT group and 3200 mm (range 2300 mm) in the sham group (p ¼ 0.639). Visual acuity (VA) was similar, with a median of 0.2 (minimumÀmaximum 0.08À0.5) in the TTT group and a median of 0.16 (minÀmax 0.10À0.32) in the sham group. A total of 21 patients were followed for 1 year, 13 in the TTT group (2.7 treatments/patient) and eight in the sham group. Membrane diameter increased in both groups, by a median of 350 mm (range 1600 mm) in the TTT group and 800 mm (range 1700 mm) in the sham group (p ¼ 0.414), respectively, and there was a loss in VA of ! 15 letters in 5/13 patients (38%) in the TTT group compared with 2/8 patients (25%) in the sham group (p ¼ 0.266). Reading ability deteriorated equally over time in both groups. Seven patients were lost to follow-up due to reluctance to continue in the study (n ¼ 4) or development of a classical component > 50% (n ¼ 3) requiring photodynamic therapy (PDT). Conclusion:The results from this randomized, prospective pilot study of TTT for occult CNV did not indicate that TTT has a beneficial effect on visual outcome 1 year after treatment compared with the visual outcome that results from the natural course of the disease. The small study size limits statistical power and results from large control studies are needed.

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Age-Related Macular Degeneration

Cited by 62 publications

References 23 publications

Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment

Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment

Identification of Chlamydia pneumoniae within human choroidal neovascular membranes secondary to age-related macular degeneration

Transpupillary thermotherapy for occult subfoveal choroidal neovascularization: a 1‐year, prospective randomized pilot study

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