The Role of Inflammation and Infection in Age-related Macular Degeneration

Barouch, Fina C.; Miller, Joan W.

doi:10.1097/iio.0b013e3180377936

Cited by 26 publications

(12 citation statements)

References 68 publications

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“…These persistent changes, coupled with an IFN␥-driven increase in choroidal cell proliferation, suggest a pathway for the entry of choroidal neovascular blood vessels into the SRS via the RPE tight junctions. These mechanisms provide a basis for understanding the role of inflammation in choroidal neovascularization and AMD (4,50,65).…”

Section: Discussionmentioning

confidence: 99%

IFNγ regulates retinal pigment epithelial fluid transport

Maminishkis

Banzon

et al. 2009

American Journal of Physiology-Cell Physiology

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The present experiments show that IFNgamma receptors are mainly localized to the basolateral membrane of human retinal pigment epithelium (RPE). Activation of these receptors in primary cultures of human fetal RPE inhibited cell proliferation and migration, decreased RPE mitochondrial membrane potential, altered transepithelial potential and resistance, and significantly increased transepithelial fluid absorption. These effects are mediated through JAK-STAT and p38 MAPK signaling pathways. Second messenger signaling through cAMP-PKA pathway- and interferon regulatory factor-1-dependent production of nitric oxide/cGMP stimulated the CFTR at the basolateral membrane and increased transepithelial fluid absorption. In vivo experiments using a rat model of retinal reattachment showed that IFNgamma applied to the anterior surface of the eye can remove extra fluid deposited in the extracellular or subretinal space between the retinal photoreceptors and RPE. Removal of this extra fluid was blocked by a combination of PKA and JAK-STAT pathway inhibitors injected into the subretinal space. These results demonstrate a protective role for IFNgamma in regulating retinal hydration across the outer blood-retinal barrier in inflammatory disease processes and provide the basis for possible therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

IFNγ regulates retinal pigment epithelial fluid transport

Maminishkis

Banzon

et al. 2009

American Journal of Physiology-Cell Physiology

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“…26,27 During the late stage of the disease, more evidence can be found for inflammatory involvement. 25,28 The immunological protein expression profile in Ccl2…”

Section: Cx3cr1mentioning

confidence: 99%

A High Omega-3 Fatty Acid Diet Reduces Retinal Lesions in a Murine Model of Macular Degeneration

Tuo

Ross

Herzlich

et al. 2009

The American Journal of Pathology

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Age-related macular degeneration (AMD) is one of the leading cause of blindness among the elderly; however, current therapy options are limited. Epidemiological studies have shown that a diet that is high in -3 polyunsaturated (n-3) fatty acids can slow disease progression in patients with advanced AMD. In this study, we evaluated the effect of such a diet on the retinas of Ccl2 ؊/؊ /Cx3cr1 ؊/؊ mice, a model that develops AMD-like retinal lesions that include focal deep retinal lesions, abnormal retinal pigment epithelium, photoreceptor degeneration, and A2E accumulation. Ccl2 ؊/؊ /Cx3cr1 ؊/؊ mice that ingested a high n-3 fatty acid diet showed a slower progression of retinal lesions compared with the low n-3 fatty acids group. Some mice that were given high levels of n-3 fatty acids had lesion reversion. We found a shunted arachidonic acid metabolism that resulted in decreased pro-inflammatory derivatives (prostaglandin E 2 and leukotriene B 4 ) and an increased antiinflammatory derivative (prostaglandin D 2 ). We also measured lower ocular TNF-␣ and IL-6 transcript levels in the mice fed a diet of high n-3 fatty acids. Our findings in these mice are in line with human studies of AMD risk reduction by long-chain n-3 fatty acids. This murine model provides a useful tool to evaluate therapies that might delay the development of AMD.

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“…Immunohistochemical and molecular genetic evidence of chronic inflammation in affected tissue is seen in Alzheimer's disease (AD) [1], Parkinson's disease (PD) [2], multiple sclerosis (MS) [3] and in age-related macular degeneration (AMD) [4]. More than 20 epidemiological studies indicated that the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) greatly reduced the risk of AD, testifying the importance of inflammatory reaction in AD.…”

Section: Introductionmentioning

confidence: 99%

Curcumin Protects Dopaminergic Neuron Against LPS Induced Neurotoxicity in Primary Rat Neuron/Glia Culture

et al. 2008

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Using primary rat mesencephalic neuron-glia cultures as an in vitro model of Parkinson's disease (PD), we tested the effect of curcumin, a natural dietary pigment with well-known anti-inflammation effects, on dopaminergic (DA) degeneration. Curcumin pretreatment mitigated LPS-induced DA neurotoxicity in a concentration-dependent manner and curcumin post-treatment also showed protective effect. Microglia depletion abolished this protective effect of curcumin, indicating that microglia play an important role in this effect. Supportively, observation by immunocytochemistry staining using OX-42 antibody showed that curcumin treatment inhibited LPS-induced morphological change of microglia. Besides, LPS-induced production of many proinflammatory factors and their gene expressions decreased dramatically after curcumin treatment. Results also revealed that curcumin treatment decreased LPS-induced activation of two transcription factors--nuclear factors kappaB (NF-kappaB) and activator protein-1 (AP-1). Taken together, our study implicated that curcumin might be a potential preventive and therapeutic strategy for inflammation-related neurodegenerative diseases.

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The Role of Inflammation and Infection in Age-related Macular Degeneration

Cited by 26 publications

References 68 publications

IFNγ regulates retinal pigment epithelial fluid transport

IFNγ regulates retinal pigment epithelial fluid transport

A High Omega-3 Fatty Acid Diet Reduces Retinal Lesions in a Murine Model of Macular Degeneration

Curcumin Protects Dopaminergic Neuron Against LPS Induced Neurotoxicity in Primary Rat Neuron/Glia Culture

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