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ABSTRACT: Age-related macular degeneration (AMD) is a complex, degenerative and progressive disease involving multiple genetic and environmental factors. It can result in severe visual loss e.g. AMD is the leading cause of blindness in the elderly in the western countries. Although age, genetics, diet, smoking, and many cardiovascular factors are known to be linked with this disease there is increasing evidence that long-term oxidative stress, impaired autophagy clearance and inflammasome mediated inflammation are involved in the pathogenesis. Under certain conditions these may trigger detrimental processes e.g. release of vascular endothelial growth factor (VEGF), causing choroidal neovascularisation e.g. in wet AMD. This review ties together these crucial pathological threads in AMD.
The international journal of biochemistry & cell biology 04/2013; · 4.89 Impact Factor
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ABSTRACT: Age-related macular degeneration (AMD) is a complex, degenerative and progressive eye disease that usually does not lead to complete blindness, but can result in severe loss of central vision. Risk factors for AMD include age, genetics, diet, smoking, oxidative stress and many cardiovascular-associated risk factors. Autophagy is a cellular housekeeping process that removes damaged organelles and protein aggregates, whereas heterophagy, in the case of the retinal pigment epithelium (RPE), is the phagocytosis of exogenous photoreceptor outer segments. Numerous studies have demonstrated that both autophagy and heterophagy are highly active in the RPE. To date, there is increasing evidence that constant oxidative stress impairs autophagy and heterophagy, as well as increases protein aggregation and causes inflammasome activation leading to the pathological phenotype of AMD. This review ties together these crucial pathological topics and reflects upon autophagy as a potential therapeutic target in AMD.
Autophagy 04/2013; 9(7). · 7.45 Impact Factor
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ABSTRACT: Increased oxidative stress has been associated with the aging process. However, recent studies have revealed that a low-level oxidative stress can even extend the lifespan of organisms. Reactive oxygen species (ROS) are important signaling molecules, e.g., being required for autophagic degradation. SIRT1, a class III protein deacetylase, is a crucial cellular survival protein, which is also involved in combatting oxidative stress. For instance, SIRT1 can stimulate the expression of antioxidants via the FoxO pathways. Moreover, in contrast to ROS, SIRT1 inhibits NF-κB signaling which is a major inducer of inflammatory responses, e.g., with inflammasome pathway. Recent studies have demonstrated that an increased level of ROS can both directly and indirectly control the activity of SIRT1 enzyme. For instance, ROS can inhibit SIRT1 activity by evoking oxidative modifications on its cysteine residues. Decreased activity of SIRT1 enhances the NF-κB signaling, which supports inflammatory responses. This crosstalk between the SIRT1 and ROS signaling provokes in a context-dependent manner a decline in autophagy and a low-grade inflammatory phenotype, both being common hallmarks of ageing. We will review the major mechanisms controlling the signaling balance between the ROS production and SIRT1 activity emphasizing that this crosstalk has a crucial role in the regulation of the aging process.
International Journal of Molecular Sciences 01/2013; 14(2):3834-59. · 2.60 Impact Factor
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ABSTRACT: Neurodegenerative diseases are characterized by selective neuronal vulnerability and neurodegeneration in specific brain regions. The pathogenesis of these disorders centrally involves abnormal accumulation and aggregation of specific proteins, which are deposited in intracellular inclusions or extracellular aggregates that are characteristic for each disease. Increasing evidence suggests that genetic mutations or environmental factors can instigate protein misfolding and aggregation in these diseases. Consequently, neurodegenerative diseases are often considered as conformational diseases. This idea is further supported by studies implicating that impairment of the protein quality control (PQC) and clearance systems, such as the ubiquitin-proteasome system and autophagosome-lysosome pathway, may lead to the abnormal accumulation of disease-specific proteins. This suggests that similar pathological mechanisms may underlie the pathogenesis of the different neurodegenerative disorders. Interestingly, several proteins that are known to associate with neurodegenerative diseases have been identified as important regulators of PQC and clearance systems. In this review, we summarize the central features of abnormal protein accumulation in different common neurodegenerative diseases and discuss some aspects of specific disease-associated proteins regulating the PQC and clearance mechanisms, such as ubiquilin-1.
American journal of neurodegenerative disease. 01/2013; 2(1):1-14.
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ABSTRACT: Age-related macular degeneration (AMD) is an ocular disease and the main reason for sight loss in the elderly in the developed countries. The pathogenesis of the disease is complex and not fully understood, but involves several environmental and genetic risk factors. However, little is known about the role of epigenetics in this disease although it is recognized that epigenetic alterations often precede genetic changes in many pathological conditions and regulate aging and the developmental processes. There is experimental evidence for the involvement of DNA methylation and histone modifications in the pathogenesis of drusen formation, a central hallmark of AMD. However, the main impact of epigenetic modifications, including persistent lysine methylation of the H3 histone, is exerted during retinal embryonic development. This interplay opens an exciting possibility to manipulate the epigenetic pattern and to develop novel AMD therapies by physical, pharmacological or genetic interventions. One of the most intriguing questions is why different individuals develop different AMD phenotypes. Epigenetic regulation might open new perspectives into these changes in AMD pathology.
Frontiers in bioscience (Scholar edition) 01/2013; S5:412-425.
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ABSTRACT: Autophagy and apoptosis are crucial cellular housekeeping and tissue survival mechanisms. There is emerging evidence of important crosstalk between apoptosis and autophagy which can be linked to inflammasome activation. Beclin 1 is a platform protein which assembles an interactome consisting of diverse proteins which control the initiation of autophagocytosis and distinct phases in endocytosis. Recent studies have demonstrated that the anti-apoptotic Bcl-2 family members can interact with Beclin 1 and inhibit autophagy. Consequently, impaired autophagy can trigger inflammasome activation. Interestingly, the hallmarks of the ageing process include a decline in autophagy, increased resistance to apoptosis and a low-grade inflammatory phenotype. Age-related stresses, e.g. genotoxic, metabolic and environmental insults, enhance the expression of NF-κB-driven anti-apoptotic Bcl-2 proteins which repress the Beclin 1-dependent autophagy. Suppression of autophagocytosis provokes inflammation including NF-κB activation which further potentiates anti-apoptotic defence. In a context-dependent manner, this feedback defence mechanism can enhance the aging process or provoke tumorigenesis or cellular senescence. We will review the role of Beclin 1 interactome in the crosstalk between apoptosis, autophagy and inflammasomes emphasizing that disturbances in Beclin 1-dependent autophagy can have a crucial impact on the aging process.
Ageing research reviews 12/2012; · 5.62 Impact Factor
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ABSTRACT: Macroautophagy is an important route in cellular maintenance, in the breakdown and reuse intracellular of materials. It is closely related to endocytosis, the means by which the cell can absorb extracellular material, as both macroautophagy and endocytosis have converging steps and common participating molecules. The point where autophagosomes and endosomes fuse with lysosomes to permit for the final degradation of their contents is important. One of the most substantial molecules in the maturation of autophagosomes/endosomes is Rab7, a member of small GTPases. Rab7 designates the maturation of endosomes and also autophagosomes, directing the trafficking of cargos along microtubules, and finally, participating in the fusion step with lysosomes. Rab7 is an effective multifunctional regulator of autophagy and endocytosis. Since many aggregation-based diseases, e.g. age-related macular degeneration of the eye (AMD) and Alzheimer's disease are due of malfunctioning in the autophagic process, the management of Rab7 activity might hold potential as a therapeutic target against these diseases.
Biochimica et Biophysica Acta 12/2012; · 4.66 Impact Factor
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ABSTRACT: Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly in the developed countries. The number of AMD patients will double during the next decades due to increasing number of aged people. Chronic oxidative stress, inflammation and accumulation of protein-rich deposits both in the retinal pigment epithelium lysosomes and under the retinal pigment epithelium herald the onset of AMD. The disease can be divided into dry and wet AMD forms. The dry form of the disease is more prevalent accounting for up to 90% of all cases. Continued intraocular injections are the current treatment strategy to prevent progression of wet AMD. It is a major challenge to develop new drugs that could prevent or at least ease the symptoms of the increasing population of AMD patients. Since AMD pathology is clearly associated with accumulated protein deposits, the autophagy clearance system might represent a potential future therapeutic target for AMD as is thoroughly discussed here.
Future medicinal chemistry 11/2012; 4(17):2153-61. · 2.52 Impact Factor
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ABSTRACT: Alzheimer's disease (AD) involves increased accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles as well as neuronal loss in various regions of the neocortex. Neuroinflammation is also present, but its role in AD is not fully understood. We previously showed increased levels of pro-inflammatory cytokine interleukin-18 (IL-18) in different regions of AD brains, where it co-localized with Aβ-plaques, as well as the ability of IL-18 to increase expression of glycogen synthase kinase-3β (GSK-3β) and cyclin dependent kinase 5, involved in hyperphosphorylation of tau-protein. Elevated IL-18 has been detected in several risk conditions for AD, including obesity, type-II diabetes, and cardiovascular diseases as well as in stress.
We differentiated SH-SY5Y neuroblastoma cells as neuron-like and exposed them to IL-18 for various times. We examined the protein levels of amyloid-β precursor protein (APP) and its processing products, its cleaving enzymes, involved in amyloidogenic processing of APP, and markers of apoptosis.
IL-18 increased protein levels of the β-site APP-cleaving enzyme BACE-1, the N-terminal fragment of presenilin-1 and slightly presenilin enhancer 2, both of which are members of the γ-secretase complex, as well as Fe65, which is a binding protein of the C-terminus of APP and one regulator for GSK-3β. IL-18 also increased APP expression and phosphorylation, which preceded increased BACE-1 levels. Further, IL-18 altered APP processing, increasing Aβ40 production in particular, which was inhibited by IL-18 binding protein. Increased levels of soluble APPβ were detected in culture medium after the IL-18 exposure. IL-18 also increased anti-apoptotic bcl-xL levels, which likely counteracted the minor increase of the pro-apoptotic caspase-3. Lactate dehydrogenase activity in culture medium was unaffected.
The IL-18 induction of BACE-1, APP processing, and Aβ is likely to be linked to stress-associated adaptations in neurons during the course of normal functioning and development. However, in the course of wider changes in the aging brain, and particularly in AD, the effects of heightened or prolonged levels of IL-18 may contribute to the process of AD, including via increased Aβ.
Journal of Neuroinflammation 08/2012; 9:199. · 3.83 Impact Factor
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ABSTRACT: Oxidative stress and inflammation are known to be associated with age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells play the principal role in the immune defense of macula, and their dysfunction is a crucial event leading to clinically relevant changes seen in AMD. In the present study, we have examined the ability of oxidative stress to activate inflammasome signaling in the human ARPE-19 cells by adding the lipid peroxidation end product 4-hydroxynonenal (HNE) to cell cultures pre-treated or not treated with the endotoxin, LPS. Our results indicate that LPS and HNE significantly increased the production of IL-6 and IL-18, respectively. LPS treatment preceding HNE induced an even greater increase in the production of IL-18 than HNE alone. In addition to IL-18, HNE significantly increased the production of IL-1β. The productions of IL-1β and IL-18 were reduced in the cell cultures pre-treated with the Caspase-1 inhibitor. PCR analysis revealed that HNE induced an over 5-fold increase in the amount of NLRP3 mRNA compared to control cells; LPS had no effect. In conclusion, our present data suggest that oxidative stress can activate NLRP3 inflammasomes in RPE cells which occupy center stage in the pathogenesis of AMD.
Immunology letters 06/2012; 147(1-2):29-33. · 2.91 Impact Factor
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ABSTRACT: IntroductionThe aging process represents a progressive decline in cellular and organism function. Explaining the aging process has given
rise to a cornucopia for different theories in which the basic difference has been the question whether aging is genetically
regulated or an entropic degeneration process.
DiscussionDifferent screening techniques have revealed that mammalian aging is associated with the activation of NF-κB transcription
factor system. The NF-κB system is an ancient host defense system concerned with immune responses and different external and
internal dangers, such as oxidative and genotoxic stress. NF-κB signaling is not only the master regulator of inflammatory
responses but can also regulate several homeostatic responses such as apoptosis, autophagy, and tissue atrophy. We will describe
how chronic activation of NF-κB signaling has the capacity to induce the senescent phenotype associated with aging. Interestingly,
several longevity genes such as SIRT1, SIRT6, and FoxOs can clearly suppress NF-κB signaling and in this way delay the aging
process and extend lifespan.
ConclusionIt seems that the aging process is an entropic degeneration process driven by NF-κB signaling. This process can be regulated
by a variety of longevity genes along with a plethora of other factors such as genetic polymorphism, immune and dietary aspects,
and environmental insults.
Journal of Clinical Immunology 04/2012; 29(4):397-405. · 3.08 Impact Factor
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ABSTRACT: Oxidative stress and low-grade inflammation are the hallmarks of the aging process and are even more enhanced in many age-related degenerative diseases. Mitochondrial dysfunction and oxidative stress can provoke and potentiate inflammatory responses, but the mechanism has remained elusive. Recent studies indicate that oxidative stress can induce the assembly of multiprotein inflammatory complexes called the inflammasomes. Nod-like receptor protein 3 (NLRP3) is the major immune sensor for cellular stress signals, e.g., reactive oxygen species, ceramides, and cathepsin B. NLRP3 activation triggers the caspase-1-mediated maturation of the precursors of IL-1β and IL-18 cytokines. During aging, the autophagic clearance of mitochondria declines and dysfunctional mitochondria provoke chronic oxidative stress, which disturbs the cellular redox balance. Moreover, increased NF-κB signaling observed during aging could potentiate the expression of NLRP3 and cytokine proforms enhancing the priming of NLRP3 inflammasomes. Recent studies have demonstrated that NLRP3 activation is associated with several age-related diseases, e.g., the metabolic syndrome. We will review here the emerging field of inflammasomes in the appearance of the proinflammatory phenotype during the aging process and in age-related diseases.
Cellular and Molecular Life Sciences CMLS 03/2012; 69(18):2999-3013. · 6.57 Impact Factor
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ABSTRACT: Inflammaging refers to a low-grade pro-inflammatory phenotype which accompanies aging in mammals. The aging process is associated with a decline in autophagic capacity which impairs cellular housekeeping, leading to protein aggregation and accumulation of dysfunctional mitochondria which provoke reactive oxygen species (ROS) production and oxidative stress. Recent studies have clearly indicated that the ROS production induced by damaged mitochondria can stimulate intracellular danger-sensing multiprotein platforms called inflammasomes. Nod-like receptor 3 (NLRP3) can be activated by many danger signals, e.g. ROS, cathepsin B released from destabilized lysosomes and aggregated proteins, all of which evoke cellular stress and are involved in the aging process. NLRP3 activation is also enhanced in many age-related diseases, e.g. atherosclerosis, obesity and type 2 diabetes. NLRP3 activates inflammatory caspases, mostly caspase-1, which cleave the inactive precursors of IL-1β and IL-18 and stimulate their secretion. Consequently, these cytokines provoke inflammatory responses and accelerate the aging process by inhibiting autophagy. In conclusion, inhibition of autophagic capacity with aging generates the inflammaging condition via the activation of inflammasomes, in particular NLRP3. We will provide here a perspective on the current research of the ROS-dependent activation of inflammasomes triggered by the decline in autophagic cleansing of dysfunctional mitochondria.
Aging 03/2012; 4(3):166-75. · 5.13 Impact Factor
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ABSTRACT: Adiponectin is an adipocyte-expressed protein that regulates the glucose, lipid, and energy metabolism via adiponectin receptors 1 and 2. Obesity is a known risk factor for age-related macular degeneration (AMD). We, therefore, examined associations of single nucleotide polymorphisms in Adiponectin (ADIPOQ) and Adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2) genes with the prevalence of advanced AMD in Finnish population. Thirty-seven markers for ADIPOQ, ADIPOR1 and ADIPOR2 were genotyped in a sample collection of 91 men and 177 women having exudative AMD and 18 men and 26 women having severe atrophic AMD. Patients were diagnosed by fundus photographs and fluorescein angiography. The control group (no signs of AMD in fundus photographs) consisted of 55 men and 111 women. Inclusion criteria age was over 65 years old without diabetes diagnosis. Out of the tested SNPs, rs10753929 located in intron of ADIPOR1 gene was significantly associated (p=0.0471) with AMD status when using a permutation procedure that controlled for the number of tested genotypes and genetic models. Odds ratio (OR) for the association was 1.699 (95% CI 1.192-2.423). The SNP consists of C/T alleles and the risk allele T had a minor allele frequency (MAF) of 20.4%. Distribution of proportion of cases/controls between alleles revealed an additive genetic model. Our findings reveal that rs10753929 ADIPOR1 variant is a novel candidate for AMD genetic risk factor in Finnish population.
Neuroscience Letters 02/2012; 513(2):233-7. · 2.11 Impact Factor
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ABSTRACT: The NF-κB signaling system and the autophagic degradation pathway are crucial cellular survival mechanisms, both being well conserved during evolution. Emerging studies have indicated that the IKK/NF-κB signaling axis regulates autophagy in a context-dependent manner. IKK complex and NF-κB can enhance the expression of Beclin 1 and other autophagy-related proteins and stimulate autophagy whereas as a feedback response, autophagy can degrade IKK components. Moreover, NF-κB signaling activates the expression of autophagy inhibitors (e.g., A20 and Bcl-2/xL) and represses the activators of autophagy (BNIP3, JNK1, and ROS). Several studies have indicated that NF-κB signaling is enhanced both during aging and cellular senescence, inducing a proinflammatory phenotype. The aging process is also associated with a decline in autophagic degradation. It seems that the activity of Beclin 1 initiation complex could be impaired with aging, since the expression of Beclin 1 decreases as does the activity of type III PI3K. On the other hand, the expression of inhibitory Bcl-2/xL proteins increases with aging. We will review the recent literature on the control mechanisms of autophagy through IKK/NF-κB signaling and emphasize that NF-κB signaling could be a potent repressor of autophagy with ageing.
International Journal of Cell Biology 01/2012; 2012:849541.
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ABSTRACT: In numerous clinical and experimental studies, preservatives present in eye drops have had detrimental effects on ocular epithelial cells. The aim of this study was to compare the cytotoxic and inflammatory effects of the preservative polyquaternium-1 (PQ-1) containing Travatan (travoprost 0.004%) and Systane Ultra eye drops with benzalkonium chloride (BAK) alone or BAK-preserved Xalatan (0.005% latanoprost) eye drops in HCE-2 human corneal epithelial cell culture.
HCE-2 cells were exposed to the commercial eye drops Travatan, Systane Ultra, Xalatan, and the preservative BAK. Cell viability was determined using colorimetric MTT (3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and by release of lactate dehydrogenase (LDH). Induction of apoptosis was measured with a using a colorimetric caspase-3 assay kit. DNA binding of the nuclear factor kappa B (NF-κB) transcription factor, and productions of the proinflammatory cytokines, interleukins IL-6 and IL-8, were determined using an enzyme-linked immunosorbent assay (ELISA) method.
Cell viability, as measured by the MTT assay, declined by up to 50% after exposure to Travatan or Systane Ultra solutions which contain 0.001% PQ-1. BAK at 0.02% rather than at 0.001% concentration evoked total cell death signs on HCE-2 cells. In addition, cell membrane permeability, as measured by LDH release, was elevated by sixfold with Travatan and by a maximum threefold with Systane Ultra. Interestingly, Travatan and Systane Ultra activated NF-κB and elevated the secretion of inflammation markers IL-6 by 3 to eightfold and IL-8 by 1.5 to 3.5 fold, respectively, as analyzed with ELISA.
Eye drops containing PQ-1 evoke cytotoxicity and enhance the NF-κB driven inflammation reaction in cultured HCE-2 cells. Our results indicate that these harmful effects of ocular solutions preserved with PQ-1 should be further evaluated in vitro and in vivo.
Molecular vision 01/2012; 18:1189-96. · 2.20 Impact Factor
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ABSTRACT: The pathogenesis of age-related macular degeneration (AMD) is complex and involves interactions between environmental and genetic factors, with oxidative stress playing an important role inducing damage in biomolecules, including DNA. Therefore, genetic variability in the components of DNA repair systems may influence the ability of the cell to cope with oxidative stress and in this way contribute to the pathogenesis of AMD. However, few reports have been published on this subject so far. We demonstrated that the c.977C>G polymorphism (rs1052133) in the hOGG1 gene and the c.972G>C polymorphism (rs3219489) in the MUTYH gene, the products of which play important roles in the repair of oxidatively damaged DNA, might be associated with the risk of AMD. Oxidative stress may promote misincorporation of uracil into DNA, where it is targeted by several DNA glycosylases. We observed that the g.4235T>C (rs2337395) and c.-32A>G (rs3087404) polymorphisms in two genes encoding such glycosylases, UNG and SMUG1, respectively, could be associated with the occurrence of AMD. Polymorphisms in some other DNA repair genes, including XPD (ERCC2), XRCC1 and ERCC6 (CSB) have also been reported to be associated with AMD. These data confirm the importance of the cellular reaction to DNA damage, and this may be influenced by variability in DNA repair genes, in AMD pathogenesis.
International Journal of Molecular Sciences 01/2012; 13(10):13378-97. · 2.60 Impact Factor
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ABSTRACT: Efficient control of energy metabolic homeostasis, enhanced stress resistance, and qualified cellular housekeeping are the hallmarks of improved healthspan and extended lifespan. AMPK signaling is involved in the regulation of all these characteristics via an integrated signaling network. Many studies with lower organisms have revealed that increased AMPK activity can extend the lifespan. Experiments in mammals have demonstrated that AMPK controls autophagy through mTOR and ULK1 signaling which augment the quality of cellular housekeeping. Moreover, AMPK-induced stimulation of FoxO/DAF-16, Nrf2/SKN-1, and SIRT1 signaling pathways improves cellular stress resistance. Furthermore, inhibition of NF-κB signaling by AMPK suppresses inflammatory responses. Emerging studies indicate that the responsiveness of AMPK signaling clearly declines with aging. The loss of sensitivity of AMPK activation to cellular stress impairs metabolic regulation, increases oxidative stress and reduces autophagic clearance. These age-related changes activate innate immunity defence, triggering a low-grade inflammation and metabolic disorders. We will review in detail the signaling pathways of this integrated network through which AMPK controls energy metabolism, autophagic degradation and stress resistance and ultimately the aging process.
Ageing research reviews 12/2011; 11(2):230-41. · 5.62 Impact Factor
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ABSTRACT: The major hallmark of cellular senescence is an irreversible cell cycle arrest and thus it is a potent tumor suppressor mechanism. Genotoxic insults, e.g. oxidative stress, are important inducers of the senescent phenotype which is characterized by an accumulation of senescence-associated heterochromatic foci (SAHF) and DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS). Interestingly, senescent cells secrete pro-inflammatory factors and thus the condition has been called the senescence-associated secretory phenotype (SASP). Emerging data has revealed that NF-κB signaling is the major signaling pathway which stimulates the appearance of SASP. It is known that DNA damage provokes NF-κB signaling via a variety of signaling complexes containing NEMO protein, an NF-κB essential modifier, as well as via the activation of signaling pathways of p38MAPK and RIG-1, retinoic acid inducible gene-1. Genomic instability evoked by cellular stress triggers epigenetic changes, e.g. release of HMGB1 proteins which are also potent enhancers of inflammatory responses. Moreover, environmental stress and chronic inflammation can stimulate p38MAPK and ceramide signaling and induce cellular senescence with pro-inflammatory responses. On the other hand, two cyclin-dependent kinase inhibitors, p16INK4a and p14ARF, are effective inhibitors of NF-κB signaling. We will review in detail the signaling pathways which activate NF-κB signaling and trigger SASP in senescent cells.
Cellular signalling 12/2011; 24(4):835-45. · 4.09 Impact Factor
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ABSTRACT: Age-related macular degeneration (AMD) is the most common reason for blindness in developed countries. AMD essentially involves chronic oxidative stress, increased accumulation of lipofuscin in retinal pigment epithelial (RPE) cells, and extracellular drusen formation, as well as presence of chronic inflammation in the retina. The capacity to prevent the accumulation of cellular cytotoxic protein aggregates is decreased in senescent cells, which may evoke lipofuscin accumulation into lysosomes in postmitotic RPE cells. The formation of lipofuscin, in turn, decreases the lysosomal enzyme activity and impairs the autophagic clearance of damaged proteins destined for cellular removal. 5'-Adenosine monophosphate-activated protein kinase (AMPK) is a well-known inhibitor of mammalian target of rapamycin (mTOR) that subsequently evokes induction of autophagy. This review examines the novel potential therapeutic targets on the AMPK-mTOR axis and the ways in which autophagy clearance can suppress or prevent RPE degeneration and development of AMD.
Rejuvenation Research 12/2011; 14(6):651-60. · 3.83 Impact Factor
