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1.
Mol Med Rep ; 23(3)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33495823

RESUMO

Age­related macular degeneration (AMD) progression occurs due to oxidative stress in retinal pigment epithelium (RPE) cells. To develop a new model of AMD, the present study investigated the effects of potassium bromate (KBrO3) on ARPE­19 cells. Incubation with KBrO3 for 24 h significantly decreased ARPE­19 cell viability in a concentration­dependent manner compared with the control group. The MTT and lactate dehydrogenase assay results indicated that KBrO3 induced cell apoptosis. Compared with the control group, KBrO3 treatment significantly decreased the Bcl2/Bax ratio, as determined via western blotting, and caspase­3 mRNA expression levels. Fluorescence microscopy indicated the increased ROS levels in cells treated with KBrO3. Endogenous antioxidant enzyme activities, including superoxide dismutase and glutathione peroxidase, were significantly inhibited by KBrO3 compared with the control group. Moreover, the antioxidants tiron and phloroglucinol inhibited KBrO3­mediated effects on ARPE­19 cells in a dose­dependent manner. Additionally, GPR109A is the binding site of 4­hydroxynonenal (4­HNE). KBrO3 displayed cytotoxic effects in 293 cells, which naturally lack the GPR109A gene, but these effects were not observed in 4­HNE­treated 293 cells, suggesting that KBrO3 induced apoptosis without increasing endogenous 4­HNE levels in cells. Moreover, the results suggested that KBrO3­induced oxidative stress may activate STAT3 to increase VEGF expression in ARPE­19 cells. Collectively, the results of the present study supported the potential use of KBrO3 to induce an in vitro model of AMD in ARPE­19 cells.


Assuntos
Apoptose/efeitos dos fármacos , Bromatos/toxicidade , Degeneração Macular , Modelos Biológicos , Caspase 3/biossíntese , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Degeneração Macular/induzido quimicamente , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese
2.
Biomed Pharmacother ; 133: 111041, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378949

RESUMO

Poly (ADP-ribose) polymerase 1 (PARP1)-dependent cell death in the retinal pigment epithelium (RPE) is implicated in dry age-related macular degeneration (AMD). Although PARP1 inhibitors are available for treating dry AMD, their delivery route is not ideal for patients. The aim of this study was to test the efficacy of a novel PARP1-inhibitory compound (PIC) in vitro and in vivo. This study presents PIC, a novel small molecule, with superior efficacy to PARP1 inhibitors in the market. PIC demonstrated a distinctive inhibitory profile against PARP isotypes than the FDA-approved PARP1 inhibitors. PIC inhibited PARP1 activation at an IC50 of 0.41 ± 0.15 nM in an enzyme-based assay in vitro and at IC50 and EC50 in ARPE-19 cells of 0.11 ± 0.02 nM and 0.22 ± 0.02 nM, respectively, upon H2O2 insult. PIC also moderated mitochondrial fission and depolarization and maintained cellular energy levels under oxidative stress in ARPE-19 cells. Furthermore, PIC demonstrated good corneal penetration in a rat model, presenting PIC as a promising candidate for eye drop therapeutics for dry AMD. When PIC was administered as an eye drop formulation, RPE morphology was preserved, maintaining the thickness of the outer nuclear layers under sodium iodate (SI) treatment in rats. In SI-treated rabbits, eye drop administration of PIC also retained the structural and functional integrity when analyzed using funduscopy and electroretinogram. Collectively, our data portray PIC as an attractive treatment measure for dry AMD.


Assuntos
Degeneração Macular/tratamento farmacológico , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Administração Oftálmica , Animais , Antioxidantes/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Humanos , Iodatos , Degeneração Macular/induzido quimicamente , Degeneração Macular/enzimologia , Degeneração Macular/patologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Absorção Ocular , Soluções Oftálmicas , Estresse Oxidativo/efeitos dos fármacos , Poli(ADP-Ribose) Polimerase-1/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Coelhos , Ratos Sprague-Dawley , Epitélio Pigmentado da Retina/enzimologia , Epitélio Pigmentado da Retina/patologia
3.
Curr Opin Ophthalmol ; 31(6): 563-571, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33002988

RESUMO

PURPOSE OF REVIEW: The purpose of this article is to provide an overview of drug-induced maculopathies including their clinical presentations, diagnostic findings, and treatment options. With the increasing pace of development and arrival of drugs to the market, this review aims to inform retina specialists of relevant side effects that may be encountered in a clinical practice setting. RECENT FINDINGS: The major themes visited in this article focus on relevant findings of drugs that cause pigmentary and crystalline maculopathy, photoreceptor dysfunction, cystoid macular edema, central serous choroidopathy, uveitis, and vascular damage. SUMMARY: The current review reports updated findings and discusses the pathophysiologic mechanisms, presentations, and treatments of drug-induced maculopathies.


Assuntos
Degeneração Macular/induzido quimicamente , Humanos , Edema Macular/fisiopatologia , Uveíte
4.
J Fr Ophtalmol ; 43(8): 727-730, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32620415

RESUMO

We report a case of a patient treated with tamoxifen 20mg daily as hormone therapy for breast cancer. On regular ophthalmological follow-up, tamoxifen maculopathy was detected on SD-OCT (Spectral Domain Optic Coherence Tomography, Carl Zeiss Meditec®), so the medication was discontinued. Despite discontinuation of the medication, the maculopathy progressed over time. We have been following our patient for seven years. Tamoxifen may produce a toxic maculopathy which may progress despite discontinuation of the medication. We consider our case interesting, given the lengthy follow-up of the patient with sequential SD-OCT images. To the best of our knowledge, our case represents the longest follow-up period for a patient with tamoxifen maculopathy. Moreover, we would like to stress the importance of screening in asymptomatic patients on this medication, in order to detect early pathological signs.


Assuntos
Monitorização Fisiológica , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/diagnóstico , Tamoxifeno/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Angiofluoresceinografia , Seguimentos , Humanos , Macula Lutea/efeitos dos fármacos , Macula Lutea/patologia , Degeneração Macular/induzido quimicamente , Degeneração Macular/diagnóstico , Degeneração Macular/patologia , Monitorização Fisiológica/métodos , Doenças Retinianas/patologia , Tamoxifeno/administração & dosagem , Tomografia de Coerência Óptica
5.
Obstet Gynecol ; 135(5): 1091-1094, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32282604

RESUMO

Recent studies have implicated long-term pentosan polysulfate use with vision loss from a newly described macular condition. Affected patients report difficulty with reading and adjusting to dim lighting, and they occasionally develop severe visual disability. Macular changes resemble those seen in age-related macular degeneration, potentially leading to misdiagnosis. The objectives of this Current Commentary are to summarize studies evaluating the association between pentosan polysulfate use and macular disease, to educate pentosan polysulfate prescribers about the clinical manifestations of this condition, and to provide recommendations for screening at-risk patients.


Assuntos
Cistite Intersticial/tratamento farmacológico , Degeneração Macular/induzido quimicamente , Poliéster Sulfúrico de Pentosana/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade
6.
Z Rheumatol ; 79(2): 186-194, 2020 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-32095892

RESUMO

BACKGROUND: Antimalarial medication (AM) plays an important role in the treatment of rheumatic diseases. OBJECTIVE: Updated evidence-based recommendations on the safety management of rheumatological treatment with AM are presented. METHODS: A systematic literature search in the databases Medline (PubMed) and Cochrane identified 1160 studies on the safety of treatment with AM in rheumatology. In addition, a manual search was carried out and 67 publications considered to be particularly relevant by the authors were analyzed in more detail. These publications served as a basis for consensus-based recommendations. RESULTS: Treatment with AM in rheumatology should be carried out with hydroxychloroquine (HCQ) with a dosage not exceeding 5 mg/kg body weight/day. Patients should undergo a basic ophthalmological examination within the first 6 months of AM treatment. Pre-existing maculopathy, renal insufficiency (glomerular filtration rate, GFR <60 ml/min), tamoxifen comedication, a daily dose of >5 mg/kg HCQ or treatment with chloroquine (CQ) show an increased risk for AM-induced retinopathy. These patients should undergo an annual ophthalmological check from the beginning of the treatment, whereas patients with no risk factors are recommended to start this only after 5 years of taking the medication. The ophthalmological examination should comprise at least both an appropriate subjective and an objective method and these are usually an automated visual field test and optical coherence tomography (OCT). A visual field test revealing a parafoveal sensitivity loss and an OCT showing a parafoveal circumscribed loss of the photoreceptor layer or focal interruptions of the structural line of the outer segment are signs of a possible AM retinopathy. Determination of creatine kinase (CK) and lactate dehydrogenase (LDH) in blood is appropriate to screen for cardiomyopathy and myopathy and should be checked before starting the treatment and then ca. every 3 months. The use of cardiac biomarkers, such as brain natriuretic peptide (BNP) or troponin in serum, electrocardiograph (ECG) or cardiac imaging should be considered depending on the situation. An intake of HCQ is safe during pregnancy and breastfeeding according to the current state of knowledge and is protective for mother and child in patients with systemic lupus erythematosus. CONCLUSION: The updated recommendations on AM treatment in rheumatology in particular include a more rigorous measuring of doses, risk stratification in monitoring and defined ophthalmological examination methods to detect a possible retinopathy.


Assuntos
Antimaláricos , Antirreumáticos , Degeneração Macular/induzido quimicamente , Doenças Reumáticas/tratamento farmacológico , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Criança , Humanos , Hidroxicloroquina , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Reumatologia , Gestão da Segurança
7.
Drugs Aging ; 37(4): 311-320, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32026309

RESUMO

BACKGROUND AND OBJECTIVE: There is a relative lack of head-to-head comparisons of denosumab against other osteoporosis drugs on safety. We aimed to explore ocular outcomes in patients with osteoporosis initiating denosumab vs zoledronic acid. METHODS: We conducted a cohort study using claims data (2010-15) from two large US commercial insurance databases including patients with osteoporosis who were aged 50 years or older and initiators of denosumab or zoledronic acid. The primary outcomes were (1) receipt of cataract surgery and development of (2) wet age-related macular degeneration and (3) dry age-related macular degeneration within 365 days after initiation of denosumab vs zoledronic acid. Propensity score fine stratification and weighting were used to control for potential confounding, and we calculated the incidence rate and hazard ratio for each outcome in the cohorts. The estimates from the two databases were combined with a fixed-effects model meta-analysis. RESULTS: The study cohort included 50,821 denosumab and 67,471 zoledronic acid initiators. In the propensity score-weighted analysis, compared to zoledronic acid use, denosumab was associated with a modestly decreased risk of undergoing cataract surgery (hazard ratio 0.91; 95% confidence interval 0.85-0.98) but not with the risk of wet age-related macular degeneration (hazard ratio 1.29; 95% confidence interval 0.99-1.70) or dry age-related macular degeneration (hazard ratio 1.03; 95% confidence interval 0.98-1.09). CONCLUSIONS: In this large population-based cohort study of 118,292 patients with osteoporosis, initiation of denosumab was associated with a modestly decreased risk of cataract surgery vs zoledronic acid. The risk of age-related macular degeneration was similar between the two drugs.


Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Extração de Catarata/estatística & dados numéricos , Bases de Dados Factuais , Denosumab/efeitos adversos , Degeneração Macular/induzido quimicamente , Osteoporose/tratamento farmacológico , Ácido Zoledrônico/efeitos adversos , Idoso , Conservadores da Densidade Óssea/uso terapêutico , Estudos de Coortes , Denosumab/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Ácido Zoledrônico/uso terapêutico
8.
BMJ Case Rep ; 12(11)2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31727637

RESUMO

A patient with choroidal haemangioma in the right eye developed photodynamic therapy (PDT)-induced acute exudative maculopathy within a week of being subjected to PDT (for treating the choroidal haemangioma). The condition was managed with an intravitreal injection of bevacizumab and responded well to therapy.


Assuntos
Neoplasias da Coroide/tratamento farmacológico , Hemangioma/tratamento farmacológico , Degeneração Macular/induzido quimicamente , Fotoquimioterapia/efeitos adversos , Adulto , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Humanos , Degeneração Macular/tratamento farmacológico , Masculino , Baixa Visão/etiologia
9.
Ophthalmic Surg Lasers Imaging Retina ; 50(10): 656-659, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31671200

RESUMO

A pigmentary maculopathy associated with chronic use of the drug pentosan polysulfate sodium (PPS) was recently described. The authors present a case of PPS-associated maculopathy that continued to progress for 6 years after discontinuation of this medication. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:656-659.].


Assuntos
Anticoagulantes/efeitos adversos , Degeneração Macular/induzido quimicamente , Poliéster Sulfúrico de Pentosana/efeitos adversos , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade
11.
Exp Eye Res ; 187: 107746, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31394101

RESUMO

This review will focus on the inflammatory and toxic mechanism of action of 7-ketocholesterol (7KCh) and the potential implications of its accumulation, especially in the retina. 7KCh is a pro-inflammatory oxysterol usually associated with oxidized lipoprotein deposits present in aged retinas. High amounts of 7KCh can be generated in situ in these lipoprotein deposits possibly through a free radical-mediated mechanism catalyzed by iron. 7KCh seems to activate several kinase signaling pathways that work via multiple transcription factors to induce cytokines and intracellular effectors causing cell death. There seems to be a controversy in the literature in relation to the mechanisms of death induced by 7KCh. Some of the discrepancies arise from the way the oxysterol is delivered because different signaling pathways are activated in different experimental setups. The elucidation of the inflammatory and toxic mechanisms is crucial for the discovery and design of new therapies. Importantly, there is little evidence of 7KCh detoxifying mechanisms in the retina, although some potential enzymes have been described. Thus, continuous formation throughout life and potential toxicity of 7KCh points it out as an "age-related" risk factor in pathologies such as age-related macular degeneration.


Assuntos
Inibidores Enzimáticos/toxicidade , Cetocolesteróis/toxicidade , Degeneração Macular/induzido quimicamente , Retina/efeitos dos fármacos , Retinite/induzido quimicamente , Animais , Morte Celular , Humanos , Inflamação , Degeneração Macular/patologia , Oxirredução , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/patologia , Retinite/patologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-30857240

RESUMO

This study provides diverse lines of evidence demonstrating that fluoride (F) exposure contributes to degenerative eye diseases by stimulating or inhibiting biological pathways associated with the pathogenesis of cataract, age-related macular degeneration and glaucoma. As elucidated in this study, F exerts this effect by inhibiting enolase, τ-crystallin, Hsp40, Na⁺, K⁺-ATPase, Nrf2, γ -GCS, HO-1 Bcl-2, FoxO1, SOD, PON-1 and glutathione activity, and upregulating NF-κB, IL-6, AGEs, HsP27 and Hsp70 expression. Moreover, F exposure leads to enhanced oxidative stress and impaired antioxidant activity. Based on the evidence presented in this study, it can be concluded that F exposure may be added to the list of identifiable risk factors associated with pathogenesis of degenerative eye diseases. The broader impact of these findings suggests that reducing F intake may lead to an overall reduction in the modifiable risk factors associated with degenerative eye diseases. Further studies are required to examine this association and determine differences in prevalence rates amongst fluoridated and non-fluoridated communities, taking into consideration other dietary sources of F such as tea. Finally, the findings of this study elucidate molecular pathways associated with F exposure that may suggest a possible association between F exposure and other inflammatory diseases. Further studies are also warranted to examine these associations.


Assuntos
Catarata/metabolismo , Fluoretos/administração & dosagem , Glaucoma/metabolismo , Degeneração Macular/metabolismo , Saúde Pública , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Catarata/induzido quimicamente , Catarata/fisiopatologia , Fluoretação , Fluoretos/efeitos adversos , Glaucoma/induzido quimicamente , Glaucoma/fisiopatologia , Humanos , Degeneração Macular/induzido quimicamente , Degeneração Macular/fisiopatologia , Saúde Bucal , Estresse Oxidativo , Abastecimento de Água
17.
Arch Toxicol ; 93(2): 453-465, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30426163

RESUMO

Lesion to the retinal pigment epithelium (RPE) is a crucial event in the development of age-related macular degeneration (AMD), the leading cause of blindness in industrialized countries. Tobacco smoking and high-energy visible blue (HEV; 400-500 nm) light exposure are major environmental risk factors for AMD. Individually, they have been shown to cause damage to the RPE. Tobacco smoke contains toxic polycyclic aromatic hydrocarbons (PAH) that can accumulate in RPE and which absorb HEV light. It can thus be postulated that the interaction between both factors in RPE cells can have a synergic toxic effect to the RPE. To test this hypothesis, cultured human RPE cells (ARPE19) were treated with nanomolar concentrations of benzo[a]pyrene (BaP) or indeno[1,2,3-cd]pyrene (IcdP), then exposed to HEV light using an irradiation system that mimics the solar spectrum normally transmitted to the retina through the human ocular media. Using mitochondrial network morphology changes and key features of AMD-related RPE defects such as apoptotic cell death and oxidative stress, we demonstrate that a synergistic phototoxicity is generated when nanomolar concentrations (≤ 500 nM) of IcdP interact with sub-lethal amounts of HEV light. Indeed, we found IcdP to be at least 3000 times more toxic for RPE cells when irradiated with HEV light. This synergy translates into disruption of mitochondrial network, ROS enhanced accumulation and apoptosis of RPE cells. Our results underline an important interplay between two environmental risk factors involved in AMD progression and strongly indicate that IcdP, upon interaction with HEV light, may initiate the biological mechanisms underlying the association between cigarette smoking and AMD-related RPE degeneration.


Assuntos
Fumar Cigarros/efeitos adversos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Benzo(a)pireno/toxicidade , Morte Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Luz/efeitos adversos , Degeneração Macular/induzido quimicamente , Degeneração Macular/etiologia , Degeneração Macular/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo , Pirenos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/metabolismo
18.
Ned Tijdschr Geneeskd ; 1632018 12 17.
Artigo em Holandês | MEDLINE | ID: mdl-30570930

RESUMO

BACKGROUND: Chloroquine (CQ) and hydroxychloroquine (HCQ) can induce retinopathy. The risk of this severe, irreversible ophthalmological complication significantly increases with duration of treatment (> 5 years) and dosage of medication (for CQ > 2.3 mg/kg/day and HCQ > 5.0 mg/kg/day). Other important risk factors are renal failure, concomitant tamoxifen use and pre-existing retinopathy or maculopathy. CASE DESCRIPTION: We describe a 46-year old woman with chronic discoid lupus erythematosus who developed bull's-eye maculopathy as a consequence of treatment with CQ in varying doses of 100-300 mg/day for five years. Treatment with CQ was subsequently discontinued. CONCLUSION: All patients treated with CQ or HCQ should be referred to the ophthalmologist for baseline testing within 1 year after starting treatment. If there are no risk factors, patients who are treated with CQ or HCQ should undergo annual ophthalmological testing from 1 year, respectively 5 years after start of treatment. The risk factors need to be rechecked at each outpatient check-up because these factors can affect the required frequency of ophthalmological check-ups.


Assuntos
Antirreumáticos/efeitos adversos , Cloroquina/efeitos adversos , Lúpus Eritematoso Discoide/tratamento farmacológico , Degeneração Macular/induzido quimicamente , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Pessoa de Meia-Idade
19.
JCI Insight ; 3(17)2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30185655

RESUMO

Advanced age-related macular degeneration (AMD), the leading cause of blindness among people over 50 years of age, is characterized by atrophic neurodegeneration or pathologic angiogenesis. Early AMD is characterized by extracellular cholesterol-rich deposits underneath the retinal pigment epithelium (RPE) called drusen or in the subretinal space called subretinal drusenoid deposits (SDD) that drive disease progression. However, mechanisms of drusen and SDD biogenesis remain poorly understood. Although human AMD is characterized by abnormalities in cholesterol homeostasis and shares phenotypic features with atherosclerosis, it is unclear whether systemic immunity or local tissue metabolism regulates this homeostasis. Here, we demonstrate that targeted deletion of macrophage cholesterol ABC transporters A1 (ABCA1) and -G1 (ABCG1) leads to age-associated extracellular cholesterol-rich deposits underneath the neurosensory retina similar to SDD seen in early human AMD. These mice also develop impaired dark adaptation, a cardinal feature of RPE cell dysfunction seen in human AMD patients even before central vision is affected. Subretinal deposits in these mice progressively worsen with age, with concomitant accumulation of cholesterol metabolites including several oxysterols and cholesterol esters causing lipotoxicity that manifests as photoreceptor dysfunction and neurodegeneration. These findings suggest that impaired macrophage cholesterol transport initiates several key elements of early human AMD, demonstrating the importance of systemic immunity and aging in promoting disease manifestation. Polymorphisms in genes involved with cholesterol transport and homeostasis are associated with a significantly higher risk of developing AMD, thus making these studies translationally relevant by identifying potential targets for therapy.


Assuntos
Cegueira/induzido quimicamente , Cegueira/metabolismo , Colesterol/metabolismo , Degeneração Macular/induzido quimicamente , Degeneração Macular/metabolismo , Monócitos/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Cegueira/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Ésteres do Colesterol/metabolismo , Progressão da Doença , Deleção de Genes , Humanos , Imunidade Inata , Degeneração Macular/imunologia , Degeneração Macular/patologia , Camundongos , Camundongos Knockout , Proteínas dos Microfilamentos/metabolismo , Oxisteróis/metabolismo , Células Fotorreceptoras de Vertebrados/metabolismo , Células Fotorreceptoras de Vertebrados/patologia , Receptores Acoplados a Proteínas-G/metabolismo , Retina/anormalidades , Retina/metabolismo , Retina/patologia , Epitélio Pigmentado da Retina/anormalidades , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia
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