Polymorphisms in CYP2C8 and CYP3A5 genes in the Nigerian population.

Drug Metab Pharmacokinet. 2016 Sep 14;:

Authors: Adehin A, Bolaji OO, Kennedy MA

Abstract
Polymorphisms in CYP2C8 and CYP3A5 genes have implications for responses elicited by the ingestion of some xenobiotics, the metabolism of which are mediated by these enzymes. CYP2C8*2, CYP2C8*3, CYP3A5*3, CYP3A5*6 and CYP3A5*7 are a few functionally-relevant variants of these genes which this study provides data for, in the Nigerian population. Blood samples were processed for genomic DNA from 178 unrelated subjects spread across Nigerian ethnicities and screened for these polymorphism through the Sequenom iPLEX MassARRAY platform. Results obtained were further validated with Sanger sequencing of a few samples and thereafter, the genotype data were statistically processed. All alleles were in Hardy-Weinberg equilibrium and CYP2C8*2 occurred at a frequency (95% CI) of 0.194 (0.154, 0.239), while CYP3A5*3, CYP3A5*6 and CYP3A5*7 were found at frequencies (95% CI) of 0.160 (0.124, 0.202), 0.096 (0.067, 0.131) and 0.126 (0.094, 0.166), respectively. However, CYP2C8*3 was not detected in the population. The study observed a 60% prevalence of carriers of at least a CYP3A5 polymorphism in the population, suggesting the probable existence of huge variability in CYP3A5 activity which may prove significant in the administration of drugs with narrow therapeutic windows and whose metabolism is largely mediated by CYP3A5.

PMID: 28427759 [PubMed - as supplied by publisher]

Learning from biomedical linked data to suggest valid pharmacogenes.

J Biomed Semantics. 2017 Apr 20;8(1):16

Authors: Dalleau K, Marzougui Y, Da Silva S, Ringot P, Ndiaye NC, Coulet A

Abstract
BACKGROUND: A standard task in pharmacogenomics research is identifying genes that may be involved in drug response variability, i.e., pharmacogenes. Because genomic experiments tended to generate many false positives, computational approaches based on the use of background knowledge have been proposed. Until now, only molecular networks or the biomedical literature were used, whereas many other resources are available.
METHOD: We propose here to consume a diverse and larger set of resources using linked data related either to genes, drugs or diseases. One of the advantages of linked data is that they are built on a standard framework that facilitates the joint use of various sources, and thus facilitates considering features of various origins. We propose a selection and linkage of data sources relevant to pharmacogenomics, including for example DisGeNET and Clinvar. We use machine learning to identify and prioritize pharmacogenes that are the most probably valid, considering the selected linked data. This identification relies on the classification of gene-drug pairs as either pharmacogenomically associated or not and was experimented with two machine learning methods -random forest and graph kernel-, which results are compared in this article.
RESULTS: We assembled a set of linked data relative to pharmacogenomics, of 2,610,793 triples, coming from six distinct resources. Learning from these data, random forest enables identifying valid pharmacogenes with a F-measure of 0.73, on a 10 folds cross-validation, whereas graph kernel achieves a F-measure of 0.81. A list of top candidates proposed by both approaches is provided and their obtention is discussed.

PMID: 28427468 [PubMed - in process]

Polymorphisms of genes related to metotrexate response and toxicity in high-grade osteosarcoma.

Expert Opin Drug Metab Toxicol. 2017 01;13(1):123

Authors: Serra M, Hattinger CM

PMID: 27852114 [PubMed - indexed for MEDLINE]

Cortex Mori Radicis extract attenuates myocardial damages in diabetic rats by regulating ERS.

Biomed Pharmacother. 2017 Apr 17;90:777-785

Authors: Lian J, Chen J, Yuan Y, Chen J, Daud M Sayed M, Luo L, Zhu Y, Li S, Bu S

Abstract
Diabetic cardiomyopathy (DCM) is diagnosed when patients with diabetes develop ventricular dysfunction but do not exhibit coronary atherosclerosis or hypertension. Cortex Mori (CM) Radicis,he epidermis of the root of Morus alba L, has been traditionally used for cough treatment in oriental medicine. In this study, we investigated the protection of myocardium by CM in streptozotocin (STZ)-induced diabetic rats and the underlying mechanisms. Diabetes was induced in rats by an injection of STZ at 25mg/kg. The animals were randomly divided into 4 groups: control, diabetes, diabetes with CM treatment, diabetes with CM preventative treatment. Pathological changes were examined by hematoxylin-eosin staining. Extracellular matrix content was assessed by Masson's trichrome staining and Western blot. Endoplasmic reticulum (ER) stress-associated molecules and main components of the mitogen-activated protein kinase (MAPK) pathway were also measured by Western blot. Myocardial damages were induced by the injection of STZ as evidenced by abnormal blood glucose and pathological cardiac changes. Administration of CM markedly ameliorated myocardial damages such as cardiac hypertrophy and fibrosis. ER stress was down-regulated, and p38 and ERK were suppressed by CM. Thus, CM may have therapeutic potential in the treatment of DCM by attenuating ER stress and ERK and p38 MAPK activation.

PMID: 28427040 [PubMed - as supplied by publisher]

Inherited Variation in Vitamin D Genes and Type 1 Diabetes Predisposition.

Genes (Basel). 2017 Apr 20;8(4):

Authors: Penna-Martinez M, Badenhoop K

Abstract
The etiology and pathophysiology of type 1 diabetes remain largely elusive with no established concepts for a causal therapy. Efforts to clarify genetic susceptibility and screening for environmental factors have identified the vitamin D system as a contributory pathway that is potentially correctable. This review aims at compiling all genetic studies addressing the vitamin D system in type 1 diabetes. Herein, association studies with case control cohorts are presented as well as family investigations with transmission tests, meta-analyses and intervention trials. Additionally, rare examples of inborn errors of vitamin D metabolism manifesting with type 1 diabetes and their immune status are discussed. We find a majority of association studies confirming a predisposing role for vitamin D receptor (VDR) polymorphisms and those of the vitamin D metabolism, particularly the CYP27B1 gene encoding the main enzyme for vitamin D activation. Associations, however, are tenuous in relation to the ethnic background of the studied populations. Intervention trials identify the specific requirements of adequate vitamin D doses to achieve vitamin D sufficiency. Preliminary evidence suggests that doses may need to be individualized in order to achieve target effects due to pharmacogenomic variation.

PMID: 28425954 [PubMed - in process]

Oxidative Stress in Retinal Diseases.

Oxid Med Cell Longev. 2017;2017:4076518

Authors: Nishimura Y, Hara H, Kondo M, Hong S, Matsugi T

PMID: 28424744 [PubMed - in process]

Phenobarbital Meets Phosphorylation of Nuclear Receptors.

Drug Metab Dispos. 2017 May;45(5):532-539

Authors: Negishi M

Abstract
Phenobarbital was the first therapeutic drug to be characterized for its induction of hepatic drug metabolism. Essentially at the same time, cytochrome P450, an enzyme that metabolizes drugs, was discovered. After nearly 50 years of investigation, the molecular target of phenobarbital induction has now been delineated to phosphorylation at threonine 38 of the constitutive androstane receptor (NR1I3), a member of the nuclear receptor superfamily. Determining this mechanism has provided us with the molecular basis to understand drug induction of drug metabolism and disposition. Threonine 38 is conserved as a phosphorylation motif in the majority of both mouse and human nuclear receptors, providing us with an opportunity to integrate diverse functions of nuclear receptors. Here, I review the works and accomplishments of my laboratory at the National Institutes of Health National Institute of Environmental Health Sciences and the future research directions of where our study of the constitutive androstane receptor might take us.

PMID: 28356313 [PubMed - indexed for MEDLINE]

AKT Axis, miR-21, and RECK Play Pivotal Roles in Dihydroartemisinin Killing Malignant Glioma Cells.

Int J Mol Sci. 2017 Feb 10;18(2):

Authors: Shao YY, Zhang TL, Wu LX, Zou HC, Li S, Huang J, Zhou HH

Abstract
Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, is known to play important roles in inhibiting proliferation rate, inducing apoptosis, as well as hindering the metastasis and invasion of glioma cells, but the underlying mechanisms are still unclear so far. In this study, methyl thiazolyl tetrazolium (MTT), colony-forming, wound healing, invasion, and apoptosis assays were performed to investigate the effect of DHA on malignant glioma cells. Results showed that DHA induced apoptosis of malignant glioma cells through Protein Kinase B (AKT) axis, induced death of malignant glioma cells by downregulating miR-21, and inhibited the invasion of malignant glioma cells corresponding with up-regulation of the reversion-inducing-cysteine-rich protein with kazal motifs (RECK). These results revealed that AKT axis, miR-21, and RECK play pivotal roles in DHA killing malignant glioma cells, suggesting that DHA is a potential agent for treating glioma.

PMID: 28208619 [PubMed - indexed for MEDLINE]

Antimicrobial resistance development following surgical site infections.

Mol Med Rep. 2017 Feb;15(2):681-688

Authors: Călina D, Docea AO, Rosu L, Zlatian O, Rosu AF, Anghelina F, Rogoveanu O, Arsene AL, Nicolae AC, Drăgoi CM, Tsiaoussis J, Tsatsakis AM, Spandidos DA, Drakoulis N, Gofita E

Abstract
Surgical site infections (SSIs) determine an increase in hospitalization time and antibiotic therapy costs. The aim of this study was to identify the germs involved in SSIs in patients from the Clinical Emergency County Hospital of Craiova (SCJUC) and to assess their resistance to antimicrobials, with comparisons between surgical wards and the intensive care unit (ICU). The biological samples were subjected to classical bacteriological diagnostics. Antibiotic resistance was tested by disc diffusion. We used hierarchical clustering as a method to group the isolates based upon the antibiotic resistance profile. The most prevalent bacterial species isolated were Staphylococcus aureus (S. aureus; 50.72%), followed by Escherichia coli (E. coli; 17.22%) and Pseudomonas aeruginosa; 10.05%). In addition, at lower percentages, we isolated glucose-non-fermenting, Gram-negative bacteria and other Enterobacteriaceae. The antibiotic resistance varied greatly between species; the most resistant were the non-fermenting Gram‑negative rods. E. coli exhibited lower resistance to third generation cephalosporins, quinolones and carbapenems. By contrast, Klebsiella was resistant to many cephalosporins and penicillins, and to a certain extent to carbapenems due to carbapenemase production. The non-fermenting bacteria were highly resistant to antibiotics, but were generally sensitive to colistin. S. aureus was resistant to ceftriaxone (100%), penicillin (91.36%), amoxicillin/clavulanate (87.50%), amikacin (80.00%) and was sensitive to levofloxacin, doxycycline, gentamycin, tigecycline and teicoplanin. The Enterobacteriaceae resistance was only slightly higher in the ICU, particularly to carbapenems (imipenem, 31.20% in the ICU vs. 14.30% in the surgical wards; risk ratio = 2.182). As regards Staphylococcus species, but for non-fermenting bacteria, even if the median was almost the same, the antibiotic resistance index values were confined to the upper limit in the ICU. The data gathered from this study may help infection control teams to establish effective guidelines for antibiotic therapies in various surgical procedures, in order to minimize the risk of developing SSIs by the efficient application of the anti-infection armamentarium.

PMID: 27959419 [PubMed - indexed for MEDLINE]

Early life antibiotic use and the risk of asthma and asthma exacerbations in children.

Pediatr Allergy Immunol. 2017 Apr 19;:

Authors: Ahmadizar F, Vijverberg SJH, Arets HGM, de Boer A, Turner S, Devereux G, Arabkhazaeli A, Soares P, Mukhopadhyay S, Garssen J, Palmer CNA, de Jongste JC, Jaddoe VW, Duijts L, van Meel ER, Kraneveld AD, Maitland-van der Zee AH

Abstract
BACKGROUND: The use of antibiotic therapy early in life might influence the risk of developing asthma. Studies assessing the influence of early life antibiotic use on the risk of asthma exacerbations are limited, and the results are inconsistent. Therefore, the aim of this study was to assess the association between use of antibiotic during the first three years of life and the risk of developing childhood asthma and the occurrence of asthma exacerbations.
METHODS: Data from four large childhood cohorts were used; two population-based cohorts to study the risk of developing asthma: Generation R (n=7,393, the Netherlands) and SEATON (n=891, Scotland, UK), and two asthma cohorts to assess the risk of asthma exacerbations: PACMAN (n=668, the Netherlands) and BREATHE (n=806, Scotland, UK). Odds ratios (ORs) were derived from logistic regression analysis within each database followed by pooling the results using a fixed- or random-effect model.
RESULTS: Antibiotic use in early life was associated with an increased risk of asthma in a meta-analysis of the Generation R and SEATON data (OR: 2.18, 95% CI: 1.04-4.60; I(2) : 76.3%). There was no association between antibiotic use in early life and risk of asthma exacerbations later in life in a meta-analysis of the PACMAN and BREATHE data (OR: 0.93, 95% CI: 0.65-1.32; I(2) : 0.0%).
CONCLUSION: Children treated with antibiotic in the first three years of life are more likely to develop asthma, but there is no evidence that the exposure to antibiotic is associated with increased risk of asthma exacerbations. This article is protected by copyright. All rights reserved.

PMID: 28423467 [PubMed - as supplied by publisher]

Androgen receptor-regulated miRNA-193a-3p targets AJUBA to promote prostate cancer cell migration.

Prostate. 2017 Apr 19;:

Authors: Jia L, Gui B, Zheng D, Decker KF, Tinay I, Tan M, Wang X, Kibel AS

Abstract
Background Dysregulation of microRNA (miRNA) expression is implicated in cancer development and progression by modulating oncogenes or tumor suppressors at the post-transcriptional level. Methods To investigate the role of miRNAs in prostate cancer (PCa) progression, we performed small RNA-sequencing (RNA-seq) analysis in androgen-dependent LNCaP cells and LNCaP-derived castration-resistant prostate cancer (CRPC) C4-2B cells. For functional validation, we specifically investigated miR-193a-3p, which is highly upregulated in C4-2B cells and modulated by the androgen receptor (AR). We elucidated the role of miR-193a-3p and its downstream target gene in PCa cell migration using biochemical approaches. Results We identified a subset of differentially expressed miRNAs in C4-2B cells compared to LNCaP cells. Computational analysis shows that the targets of upregulated miRNAs are significantly associated with downregulated protein-coding mRNAs in C4-2B cells. Gene Ontology analysis further reveals that these downregulated mRNAs are significantly enriched in cell-cell adhesion functions. Downregulation of these miRNA-targeted genes may change PCa cell motility resulting in the acquisition of metastatic potential. We then focus on miR-193a-3p and demonstrate overexpression of miR-193a-3p increases cell migration through downregulating its target AJUBA. AJUBA is a LIM domain protein and contributes to the formation and stability of cadherin-mediated cell-cell adhesion. Loss of AJUBA enhances PCa migration and downregulation of AJUBA expression is observed in metastatic PCa tumors. Conclusions Our results suggest a novel AR/miR-193a-3p/AJUBA pathway implicated in PCa progression. MiR-193a-3p is a potential therapeutic target for metastatic PCa.

PMID: 28422308 [PubMed - as supplied by publisher]

Clinical-pharmacogenetic models for personalized cancer treatment: application to malignant mesothelioma.

Sci Rep. 2017 Apr 19;7:46537

Authors: Goričar K, Kovač V, Dolžan V

Abstract
Large interindividual differences in treatment outcome are observed in cancer patients undergoing chemotherapy. Our aim was to develop and validate clinical-pharmacogenetic prediction models of gemcitabine/cisplatin or pemetrexed/cisplatin treatment outcome and develop an algorithm for genotype-based treatment recommendations in malignant mesothelioma (MM). We genotyped 189 MM patients for polymorphisms in gemcitabine, pemetrexed and cisplatin metabolism, transport and drug target genes and DNA repair pathways. To build respective clinical-pharmacogenetic models, pharmacogenetic scores were assigned by rounding regression coefficients. Gemcitabine/cisplatin model was based on training group of 71 patients and included CRP, histological type, performance status, RRM1 rs1042927, ERCC2 rs13181, ERCC1 rs3212986, and XRCC1 rs25487. Patients with higher score had shorter progression-free (PFS) and overall survival (P < 0.001). This model's sensitivity was 0.615 and specificity 0.812. In independent validation group of 66 patients the sensitivity and specificity were 0.667 and 0.641, respectively. Pemetrexed/cisplatin model was based on 57 patients and included CRP, MTHFD1 rs2236225, and ABCC2 rs2273697. Patients with higher score had worse response and shorter PFS (P < 0.001). This model's sensitivity was 0.750 and specificity 0.607. In independent validation group of 20 patients the sensitivity and specificity were 0.889 and 0.500, respectively. The proposed algorithm based on these models could enable the choice of the most effective chemotherapy for 85.5% of patients and lead to improved treatment outcome in MM.

PMID: 28422153 [PubMed - in process]

The Personalization of Clopidogrel Antiplatelet Therapy: The Role of Integrative Pharmacogenetics and Pharmacometabolomics.

Cardiol Res Pract. 2017;2017:8062796

Authors: Amin AM, Sheau Chin L, Azri Mohamed Noor D, Sk Abdul Kader MA, Kah Hay Y, Ibrahim B

Abstract
Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients undergoing percutaneous coronary intervention. However, the variable platelets reactivity response to clopidogrel may lead to outcome failure and recurrence of cardiovascular events. Although many genetic and nongenetic factors are known, great portion of clopidogrel variable platelets reactivity remain unexplained which challenges the personalization of clopidogrel therapy. Current methods for clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and platelets function testing. However, these methods lack precise prediction of clopidogrel outcome, often leading to insufficient prediction. Pharmacometabolomics which is an approach to identify novel biomarkers of drug response or toxicity in biofluids has been investigated to predict drug response. The advantage of pharmacometabolomics is that it does not only predict the response but also provide extensive information on the metabolic pathways implicated with the response. Integrating pharmacogenetics with pharmacometabolomics can give insight on unknown genetic and nongenetic factors associated with the response. This review aimed to review the literature on factors associated with the variable platelets reactivity response to clopidogrel, as well as appraising current methods for the personalization of clopidogrel therapy. We also aimed to review the literature on using pharmacometabolomics approach to predict drug response, as well as discussing the plausibility of using it to predict clopidogrel outcome.

PMID: 28421156 [PubMed]

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Therapeutic monitoring of amiodarone: pharmacokinetics and evaluation of the relationship between effect and dose/concentration.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017 Mar 31;:

Authors: Hrudikova Vyskocilova E, Grundmann M, Duricova J, Kacirova I

Abstract
Amiodarone is the most effective agent in the therapy of arrhythmias. However, the clinical effect of acute and chronic treatment is unclear and there are differences irrespective of comparable plasma/myocardial amiodarone and its metabolite desethylamiodarone concentations as well. Its unusual pharmacokinetics results in interindividual variation in plasma levels. The association between amiodarone and desethylamiodarone plasma levels and clinical efficacy is difficult to evaluate. This review was carried out to assess whether there is any objective correlation between amiodarone and desethylamiodarone plasma levels and the clinical effect. We summarized the results of relevant studies and clarified the relationship between plasma levels and effect vis á vis the pharmacokinetics and pharmacogenetics of this drug. Certain correlation was seen with oral amiodarone therapy, in others, plasma amiodarone levels were unrelated to therapeutic response and showed no correlation with changes in electrocardiogram or electrophysiological parametres. Several studies show that plasma concentration ranging between 0.5 and 2.5 mg/L appears to be the most effective, others demonstrate no difference between responders and non-responders. One way of interpreting plasma levels is to establish an individual patient´s effective concentration. Therapeutic drug monitoring can contribute to determining optimal concentration.

PMID: 28414390 [PubMed - as supplied by publisher]

[Pharmacometabonomics - the novel way to personalized drug therapy].

Biomed Khim. 2017 Mar;63(2):115-123

Authors: Maslov DL, Balashova EE, Lokhov PG, Archakov AI

Abstract
The review is devoted to pharmacometabonomics - a new branch of science focused on personalization of drug therapy through the comprehensive analysis of metabolites of patient's biological fluids. It considers the history of pharmacometabonomic, positioning to other "-omic" sciences, and system approach, realized by this science, in determination of individual therapeutic dose of the drugs and also a technical implementation of pharmacometabonomic based on direct mass spectrometry of blood plasma metabolites. Special attention is paid to a comparative analysis of pharmacometabonomics and other main approaches to personalized therapy in the clinic, such as pharmacogenetics and therapeutic drug monitoring. Finally, prospects of pharmacometabonomics applications in clinical practice were also discussed.

PMID: 28414282 [PubMed - in process]

Overview of Cantharidin and Its Analogues.

Curr Med Chem. 2017 Apr 14;:

Authors: Wang G, Dong J, Deng L

Abstract
Canthiridin has significant anti-cancer effects and only limited use due to its toxicity. In spite of some side effects such as hematochezia and tenesmus, cantharidin can efficiently inhibit various tumor cell lines, therefore, its importance can never be overemphasized. Several of its analogues show functions similar to cantharidin without high toxicity. In order to utilize cantharidin to treat cancer, some viable methods are found to reduce its side effects. Since cantharidin can inhibit the activity of protein phosphatases, new researches for the inhibition of protein phosphatases have been implemented. This review introduces facts about cantharidin and its analogues, including structure-activity relationship, pharmacogenomics, mechanism of action, some strategies and directions to reduce toxicity. The review also recommends some clinic applications and comparisons of toxicity of cantharidin and its derivatives from the biological perspective or molecular perspective.

PMID: 28413963 [PubMed - as supplied by publisher]

rs657075 (CSF2) Is Associated with the Disease Phenotype (BAS-G) of Ankylosing Spondylitis.

Int J Mol Sci. 2017 Jan 03;18(1):

Authors: Chen WC, Wei JC, Lu HF, Wong HS, Woon PY, Hsu YW, Huang JD, Chang WC

Abstract
Ankylosing spondylitis (AS) is a systemic autoimmune disease mainly affecting the lumbar spine and sacroiliac joints, and exhibits peripheral inflammatory arthropathy. More than 25 loci have been identified as associated with AS. Because both AS and rheumatoid arthritis (RA) are autoimmune diseases that may share some common genetic factors, we therefore examined if the newly identified RA genetic polymorphisms were associated with AS in a Taiwanese population. In this study, we enrolled 475 AS patients and 11,301 healthy subjects from a Taiwanese biobank as controls. Although none of single-nucleotide polymorphisms (SNPs) were associated with the susceptibility to AS, the AS disease index Bath AS Global (BAS-G) clinical phenotype was observed as significantly correlated to the AA genotype of rs657075 (CSF2). The significance remains after gender/age/disease duration adjustment and after group categorization by human leukocyte antigen-B 27 (HLA-B27) genotype. We further investigated the possible functions of rs657075 through bioinformatics approaches. Results revealed that polymorphism of rs657075 is able to influence the expression of acyl-CoA synthetase long-chain family member 6 (ACSL6). In conclusion, our study indicated that rs657075 (CSF2) is strongly associated with the AS disease index Bath AS Global (BAS-G) clinical phenotype.

PMID: 28054948 [PubMed - indexed for MEDLINE]

A case of severe movement disorder with GNAO1 mutation responsive to topiramate.

Brain Dev. 2017 May;39(5):439-443

Authors: Sakamoto S, Monden Y, Fukai R, Miyake N, Saito H, Miyauchi A, Matsumoto A, Nagashima M, Osaka H, Matsumoto N, Yamagata T

Abstract
We report the case of a 19-year-old female patient who had progressive chorea associated with a GNAO1 mutation. Chorea was refractory to multiple anticonvulsants, and the patient suffered from tiapride-induced neuroleptic malignant syndrome. After identification of a GNAO1 missense mutation at the age of 18years, topiramate treatment was initiated and the frequency of chorea decreased dramatically. The efficacy of topiramate may have been related to the inhibitory modulation of voltage-activated Ca(2+) channels. Given the side effects and complications associated with neuroleptics and deep brain stimulation, respectively, topiramate is recommended for the first-line management of severe chorea associated with a GNAO1 mutation.

PMID: 27916449 [PubMed - indexed for MEDLINE]

Establishment of a drug evaluation model against light-induced retinal degeneration using adult pigmented zebrafish.

J Pharmacol Sci. 2016 Jul;131(3):215-8

Authors: Saito Y, Tsuruma K, Shimazawa M, Nishimura Y, Tanaka T, Hara H

Abstract
Age-related macular degeneration (AMD) is a major cause of irreversible loss of central vision in the elderly. Zebrafish is an attractive animal model in some respects, lower cost, smaller housing facilities and easier genetic manipulation compared to rodents. The present study aimed to establish a drug evaluation method against light irradiation, as a dry AMD disease model, using adult pigmented zebrafish. Intravitreal administration of an antioxidant, N-acetylcysteine, protected against light-induced retinal degeneration in a concentration-dependent manner. We established a new drug evaluation model against light-induced retinal degeneration that can provide new knowledge about dry AMD pathology and therapy.

PMID: 27430989 [PubMed - indexed for MEDLINE]