Age-Related Macular Degeneration: Insights into Inflammatory Genes

Cascella, Raffaella; Ragazzo, Michele; Strafella, Claudia; Missiroli, Filippo; Borgiani, Paola; Angelucci, Francesco; Marsella, Lt; Cusumano, Andrea; Novelli, Giuseppe; Ricci, Federico; Giardina, Emiliano

doi:10.1155/2014/582842

Cited by 61 publications

(62 citation statements)

References 111 publications

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“…These pathophysiologic mechanisms are reviewed in H. Nazari et al / Progress in Retinal and Eye Research xxx (2015) JPRR596_proof ■ 24 June 2015 ■ 6/38 comprehensive publications (Zarbin, 2004;Ambati and Fowler, 2012;Cascella et al, 2014). Unlike in NV-AMD, where blocking a single culprit molecule (i.e.…”

Section: Non-exudative Amdmentioning

confidence: 99%

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

Nazari

Zhang

Zhu

et al. 2015

Progress in Retinal and Eye Research

177

142

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Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. AMD is classified as either neovascular (NV-AMD) or non-neovascular (NNV-AMD). Cumulative damage to the retinal pigment epithelium, Bruch's membrane, and choriocapillaris leads to dysfunction and loss of RPE cells. This causes degeneration of the overlying photoreceptors and consequential vision loss in advanced NNV-AMD (Geographic Atrophy). In NV-AMD, abnormal growth of capillaries under the retina and RPE, which leads to hemorrhage and fluid leakage, is the main cause of photoreceptor damage. Although a number of drugs (e.g., anti-VEGF) are in use for NV-AMD, there is currently no treatment for advanced NNV-AMD. However, replacing dead or dysfunctional RPE with healthy RPE has been shown to rescue dying photoreceptors and improve vision in animal models of retinal degeneration and possibly in AMD patients. Differentiation of RPE from human embryonic stem cells (hESC-RPE) and from induced pluripotent stem cells (iPSC-RPE) has created a potentially unlimited source for replacing dead or dying RPE. Such cells have been shown to incorporate into the degenerating retina and result in anatomic and functional improvement. However, major ethical, regulatory, safety, and technical challenges have yet to be overcome before stem cell-based therapies can be used in standard treatments. This review outlines the current knowledge surrounding the application of hESC-RPE and iPSC-RPE in AMD. Following an introduction on the pathogenesis and available treatments of AMD, methods to generate stem cell-derived RPE, immune reaction against such cells, and approaches to deliver desired cells into the eye will be explored along with broader issues of efficacy and safety. Lastly, strategies to improve these stem cell-based treatments will be discussed.

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Section: Non-exudative Amdmentioning

confidence: 99%

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

Nazari

Zhang

Zhu

et al. 2015

Progress in Retinal and Eye Research

177

142

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“…17 Oxidative stress and inflammation are believed to be possible mechanisms for this association. 18,19 Cigarette smoke contains thousands of toxic and carcinogenic chemicals, 20,21 which can be divided into 2 categories: the gas-phase smoke components and substances retained in the filter (referred to tar). The most common component in cigarette tar is hydroquinone (HQ), semiquinone mixture.…”

Section: Introductionmentioning

confidence: 99%

Brimonidine Can Prevent In Vitro Hydroquinone Damage on Retinal Pigment Epithelium Cells and Retinal Müller Cells

Ramírez

Cáceres-del-Carpio

Chu

et al. 2016

Journal of Ocular Pharmacology and Therapeutics

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HQ-induced toxicity is mediated through mitochondrial damaging, oxidative stress-related and necrosis-related pathways; Brimonidine significantly prevented the mitochondrial damaging and oxidative stress-related effects but had little effect on blocking the necrosis component of HQ-toxicity. Brimonidine protective effects differ between the different retinal cell types and high concentrations of Brimonidine (10×) have minimal damaging effects on human retinal cells.

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“…Inflammatory molecules (cytokines and chemokines), immune cells (macrophages), and complement proteins are also important in the development and progression of AMD (Friedman et al, 2004;Lim et al, 2012;Schwartz et al, 2012;Cascella et al, 2014;Sobrin and Seddon, 2014).…”

Section: Introductionmentioning

confidence: 99%

Next-generation sequencing analysis of the ARMS2 gene in Turkish exudative age-related macular degeneration patients

et al. 2017

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ABSTRACT. Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. It is a complex disease with both genetic and environmental risk factors. To improve clinical management of this condition, it is important to develop risk assessment and prevention strategies for environmental influences, and establish a more effective treatment approach. The aim of the present study was to investigate age-related maculopathy susceptibility protein 2 (ARMS2) gene sequences among Turkish patients with exudative AMD. In addition to 39 advanced exudative AMD patients, 250 healthy individuals for whom exome sequencing data were available were included as a control group. Patients with a history of known environmental and systemic AMD risk factors were excluded. Genomic DNA was isolated from peripheral blood and analyzed using next-generation sequencing. All coding exons of the ARMS2 gene were assessed. Three different ARMS2 sequence variations (rs10490923, rs2736911, and rs10490924) were identified in both the patient and control group. Within the control group, two further ARMS2 gene variants (rs7088128 and rs36213074) were also detected. Logistic regression analysis revealed a relationship between the rs10490924 polymorphism and AMD in the Turkish population.

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Age-Related Macular Degeneration: Insights into Inflammatory Genes

Cited by 61 publications

References 111 publications

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

Brimonidine Can Prevent In Vitro Hydroquinone Damage on Retinal Pigment Epithelium Cells and Retinal Müller Cells

Next-generation sequencing analysis of the ARMS2 gene in Turkish exudative age-related macular degeneration patients

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