Molecular genetic basis for fluoroquinolone-induced retinal degeneration in cats

Ramirez, Christina J; Minch, Jonathan D.; Gay, John; Lahmers, Sunshine; Guerra, Dan J.; Haldorson, Gary J.; Schneider, Terri; Mealey, Katrina L.

doi:10.1097/fpc.0b013e3283425f44

Cited by 47 publications

(67 citation statements)

References 28 publications

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“…Since previously, no case reports were presented for dogs, the present authors may briefly suggest that species difference might be a confounding factor involving the expression of ABCG2 transporters in dogs [16,17] .…”

Section: Discussionmentioning

confidence: 80%

“…Given the molecular findings for fluoroquinoloneinduced retinal degeneration and consecutive blindness in cats, ABCG2 transport protein deficiency was suggested as the responsible reason in feline retina [16] . Since previously, no case reports were presented for dogs, the present authors may briefly suggest that species difference might be a confounding factor involving the expression of ABCG2 transporters in dogs [16,17] .…”

Section: Discussionmentioning

confidence: 99%

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Aşırı Doz Marbofloksasin: Bir Köpekte Akut Körlük İçin Olağan Şüpheli

Akin¹,

Karademir²,

Belge³

et al. 2016

Kafkas Univ Vet Fak Derg

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In this case report, a 4 year old female terrier crossbred dog was presented with acute blindness following accidental high dose marbofloxacin administration was discussed. On initial referral to the clinic, a respiratory disease was evident, requiring antibiotic therapy and marbofloxacin (2.5 mg/kg) was prescribed. Meanwhile, patient was transferred to another veterinary practitioner specialized in large animal diseases, marbofloxacin had administered at an over dose (1050 mg/total dose through 3 days). The dog was then introduced back to our clinic with acute bilateral blindness. A diagnosis of marbofloxacin toxicity related to an overdose was made based on clinical examination and laboratory findings, excluding other relevant etiology. Dexamethasone was applied as initial treatment. In the following weeks, vision loss was eminent even without responding to bright light and not able to negotiate the obstacle course. According to the current literature, this is the first report on marbofloxacin overdose related acute blindness in dogs. Keywords: Blindness, Marbofloxacin overdose, Dog Aşırı Doz Marbofloksasin: Bir Köpekte Akut Körlük İçin Olağan Şüpheli ÖzetBu olgu sunumunda yanlışlıkla yüksek doz marbofloksasin uygulaması sonucunda 4 yaşlı, dişi, terrier melezi bir köpekte gelişen akut körlük vakası irdelenmiştir. Olgu kliniğe ilk başvurduğunda antibiyotik sağaltımı gerektiren bir solunum yolu enfeksiyonu olduğu belirlendi ve marbofloksasin (2.5 mg/kg) reçete edildi. Bu süre içerisinde, büyük hayvan hastalıkları konusunda uzmanlaşmış bir veteriner hekime götürülmüş ve marbofloksasin 3 gün boyunca aşırı dozda (1050 mg/3 gün boyunca toplam doz) uygulanmıştır. Köpek, uygulama sonrasında tekrar kliniğimize getirildiğinde akut körlük mevcuttu. Marbofloksasin toksisite tanısı, diğer ilişkili etiyoloji haricinde klinik, labaratuvar bulgular ve ilacın aşırı doz alımı temel alınarak konuldu. İlk sağaltım uygulaması olarak deksametazon uygulandı. Takip eden haftalarda görüş bozukluğunun olduğu, parlak ışığa tepki vermediği ve engellere takılmadan yürüyemediği tespit edildi. Son literatürlere göre köpeklerde marbofloksasinin aşırı doz uygulanması sonucu gelişen akut körlük ilk kez bildirilmiştir.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Aşırı Doz Marbofloksasin: Bir Köpekte Akut Körlük İçin Olağan Şüpheli

Akin¹,

Karademir²,

Belge³

et al. 2016

Kafkas Univ Vet Fak Derg

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“…The importance of ABCG2 in protecting the retina from fluoroquinolone-induced phototoxicity is dramatically illustrated in the feline species. Because of a species-wide defect, feline ABCG2 is dysfunctional [6], creating extreme susceptibility to fluoroquinolone-induced retinal degeneration and blindness [5]. Our data suggest that TKI-mediated inhibition of ABCG2 may enhance susceptibility to fluoroquinolone-induced retinal damage in other species, including humans.…”

Section: Discussionmentioning

confidence: 91%

“…The importance of ABCG2 in protecting the retina from fluoroquinolone-induced phototoxicity is dramatically illustrated in the feline species. Owing to a species-wide amino acid change, feline ABCG2 is dysfunctional, resulting in extreme susceptibility to fluoroquinolone-induced retinal degeneration and blindness [6]. Fluoroquinolones have been documented to cause ocular toxicity in other species, including humans [7,8,9].…”

Section: Introductionmentioning

confidence: 99%

Tyrosine Kinase Inhibitors Enhance Ciprofloxacin-Induced Phototoxicity by Inhibiting ABCG2

Mealey

Dassanayake²,

Burke³

2014

Oncology

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The tyrosine kinase inhibitor (TKI) class of anticancer agents inhibits ABCG2-mediated drug efflux. ABCG2 is an important component of the blood-retinal barrier, where it limits retinal exposure to phototoxic compounds such as fluoroquinolone antibiotics. Patients treated with TKIs would be expected to be at greater risk for retinal phototoxicity. Using an in vitro system, our results indicate that the TKIs gefitinib and imatinib abrogate the ability of ABCG2 to protect cells against ciprofloxacin-induced phototoxicity. We conclude that the concurrent administration of ABCG2 inhibitors with photoreactive fluoroquinolone antibiotics may result in retinal damage.

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“…The same group also demonstrated protoporphyria in these animals, indicating a role of ABCG2 in hematopoiesis, possibly through interaction with protoporphyrin IX, which was supported by further studies. Moreover, the functional relevance of ABCG2 was demonstrated in other mammals, being responsible for the accumulation of chemicals in milk [11], or being an important protector of retinal cells against toxic agents in domestics cats [12]. In human populations, certain SNPs in the ABCG2 gene have been linked to the occurrence of gout [13].…”

Section: Introductionmentioning

confidence: 99%

Functional characterization of the ABCG2 5′ non-coding exon variants: Stem cell specificity, translation efficiency and the influence of drug selection

Sándor

Jordanidisz

Schamberger

et al. 2016

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Functional characterization of the ABCG2 5' non-coding exon variants: stem cell specificity, translation efficiency and the influence of drug selection, BBA -Gene Regulatory Mechanisms (2016Mechanisms ( ), doi: 10.1016Mechanisms ( /j.bbagrm.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT2 Abstract ABCG2 is a multidrug transporter with wide substrate specificity, and is believed to protect several cell types from various xenobiotics and endobiotics. This "guardian" function is important in numerous cell types and tissue barriers but becomes disadvantageous by being responsible for the multidrug resistance phenotype in certain tumor cells. ABCG2 regulation at the protein level has already been extensively studied, however, regulation at the mRNA level, especially the functional role of the various 5' untranslated exon variants (5' UTRs) has been elusive. In the present work, we describe a comprehensive characterization of four ABCG2 mRNA variants with different exon 1 sequences, investigate drug inducibility, stem cell specificity, mRNA stability, and translation efficiency. Although certain variants (E1B and E1C) are considered as "constitutive" mRNA isoforms, we show that chemotoxic drugs significantly alter the expression pattern of distinct ABCG2 mRNA isoforms. When examining human embryonic stem cell lines, we provide evidence that variant E1A has an expression pattern coupled to undifferentiated stem cell stage, as its transcript level is regulated parallel to mRNAs of Oct4 and Nanog pluripotency marker genes. When characterizing the four exon 1 variants we found no significant differences in terms of mRNA stabilities and half-lives of the isoforms. In contrast, variant E1U showed markedly lower translation efficiency both at the total protein level or regarding the functional presence in the plasma membrane. Taken together, these results indicate that the different 5' UTR variants play an important role in cell type specific regulation and fine tuning of ABCG2 expression.

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Molecular genetic basis for fluoroquinolone-induced retinal degeneration in cats

Cited by 47 publications

References 28 publications

Aşırı Doz Marbofloksasin: Bir Köpekte Akut Körlük İçin Olağan Şüpheli

Aşırı Doz Marbofloksasin: Bir Köpekte Akut Körlük İçin Olağan Şüpheli

Tyrosine Kinase Inhibitors Enhance Ciprofloxacin-Induced Phototoxicity by Inhibiting ABCG2

Functional characterization of the ABCG2 5′ non-coding exon variants: Stem cell specificity, translation efficiency and the influence of drug selection

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