Advanced Clinical Imaging and Tissue-based Biomarkers of the Eye for Toxicology Studies in Minipigs.

Abstract:

:There is increased interest to use minipigs in ocular toxicology studies due to their anatomical similarities with human eyes and as a substitute for nonhuman primates. This requires adaptation of enhanced optical coherence tomography (OCT) techniques and of ocular relevant immunohistochemistry (IHC) or in situ hybridization (ISH) markers to porcine eyes. In this study, OCT and OCT angiography (AngioOCT) were performed on adult Göttingen minipigs. To increase structural information on retinal and choroidal vasculature, OCT data were speckle denoized and choroidal blood vessels were segmented with threshold filtering. In addition, we established a set of IHC and ISH markers on Davidson's fixed paraffin-embedded minipig eyes: neurofilament-160, neuronal nuclei, calretinin, protein kinase C-α, vimentin, glial fibrillary acidic protein, glutamine synthetase, ionized calcium-binding adaptor molecule-1, rhodopsin, synaptophysin, postsynaptic density protein-95, retinal pigment epithelium (RPE)-specific protein-65, von Willebrand factor, α-smooth muscle actin, desmin, and Ki-67, thus enabling visualization of retinal neuronal and glial cells, photoreceptors, synapses, RPE, blood vessels, myocytes, macrophages, or cell proliferation. Using ISH, transcripts of vascular endothelial growth factor A, angiopoietin-2, and endothelial tyrosine kinase were visualized. This article describes for the first time in minipig eyes speckle noise-free OCT, AngioOCT, and a set of IHC/ISH markers on Davidson's fixed paraffin-embedded tissues and helps to establish the minipig for ocular toxicology and pharmacology studies.

journal_name

Toxicol Pathol

journal_title

Toxicologic pathology

authors

Atzpodien EA,Jacobsen B,Funk J,Altmann B,Silva Munoz MA,Singer T,Gyger C,Hasler P,Maloca P

doi

10.1177/0192623315615553

subject

Has Abstract

pub_date

2016-04-01 00:00:00

pages

398-413

issue

3

eissn

0192-6233

issn

1533-1601

pii

0192623315615553

journal_volume

44

pub_type

杂志文章
  • Proceedings of the 2018 National Toxicology Program Satellite Symposium.

    abstract::The 2018 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri," was held in Indianapolis, Indiana, at the Society of Toxicologic Pathology's 37th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This arti...

    journal_title:Toxicologic pathology

    pub_type:

    doi:10.1177/0192623318800734

    authors: Elmore SA,Carreira V,Labriola CS,Mahapatra D,McKeag SR,Rinke M,Shackelford C,Singh B,Talley A,Wallace SM,Wancket LM,Willson CJ

    更新日期:2018-12-01 00:00:00

  • Longevity, body weight, and neoplasia in ad libitum-fed and diet-restricted C57BL6 mice fed NIH-31 open formula diet.

    abstract::Groups of C57BL6 mice of each sex were assigned to one of 2 dietary regimens, ad libitum (AL) or dietary restriction (DR), to study effects of food restriction on body weight, survival, and neoplasia. The AL and DR groups were subdivided into a scheduled sacrifice group for examination at 6-mo intervals, and a lifetim...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339502300503

    authors: Blackwell BN,Bucci TJ,Hart RW,Turturro A

    更新日期:1995-09-01 00:00:00

  • Human natural tumor necrosis factor alpha induces multiple endocrine and hematologic disorders in rats.

    abstract::Slc:Wistar male rats treated with human natural tumor necrosis factor alpha (hn TNF-alpha, 3 X 10(5) Japan reference units/kg intravenously) for 3 months showed histologic vacuolation of basophils in the anterior pituitary, hyperplasia of the thyroidal follicular epithelium, and hyperplasia of the testicular interstit...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339902700403

    authors: Kakinuma C,Hamada Y,Futamura Y,Kuwayama C,Shimoi A,Shibutani Y

    更新日期:1999-07-01 00:00:00

  • Emanuel Edward Klein--the father of British microbiology and the case of the animal vivisection controversy of 1875.

    abstract::The new Appendix A of the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes, which gives guidelines for accommodation and care of animals and was approved on June 15, 2006, was the main reason the authors decided to investigate the origins of the regulatio...

    journal_title:Toxicologic pathology

    pub_type: 传,历史文章,杂志文章,评审

    doi:10.1177/0192623309345871

    authors: Atalić B,Fatović-Ferencić S

    更新日期:2009-10-01 00:00:00

  • Increased incidence of hepatic foci and nodules in rats given one or two doses of 1,2-dibromoethane.

    abstract::Livers of male Sprague-Dawley rats were evaluated for foci and nodules 90 days and 16 months after one or two oral doses of 1,2-dibromoethane (DBE). Rats (190 g) were given the following oral treatments. Controls received corn oil (2.5 ml/kg) at 0 and 24 hr. DBE X 1 received corn oil at 0 hr and 75 mg DBE/kg at 24 hr....

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262338401200402

    authors: Moslen MT

    更新日期:1984-01-01 00:00:00

  • Recombinant human soluble CD4 does not inhibit immune function in cynomolgus monkeys.

    abstract::Recombinant soluble CD4 (sT4) has been shown to inhibit infectivity of HIV. Because of the role CD4 plays in the interaction of T-helper lymphocytes and cells bearing MHC Class II antigens, a potential adverse effect of therapy with sT4 is interference with lymphocyte function. To address this issue, we studied the ef...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339101900403

    authors: Bugelski PJ,Thiem PA,Truneh A,Morgan DG

    更新日期:1991-01-01 00:00:00

  • Target organ specificity of cell proliferation induced by various carcinogens.

    abstract::The target organ specificities of cell proliferation and histopathological lesion induction by 5 carcinogens having different target organs were evaluated using a multiorgan carcinogenesis bioassay. In Group 1, male F-344 rats aged 6 wk were sequentially treated with N-diethylnitrosamine (DEN, single 100-mg/kg ip inje...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339302100502

    authors: Yoshida Y,Tatematsu M,Takaba K,Iwasaki S,Ito N

    更新日期:1993-09-01 00:00:00

  • Dose-dependent renal tubular toxicity of harman and norharman in male F344 rats.

    abstract::The renal toxicity of harman and norharman, administered for 2 or 4 weeks at dietary levels of 1,000, 500, or 0 parts per million (ppm), was investigated in 6-week-old male F344/DuCrj rats. Although rats fed 1,000 ppm harman or norharman, but not the 500 ppm level, demonstrated marked body weight retardation from 1 we...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339202000206

    authors: Hagiwara A,Asakawa E,Kurata Y,Sano M,Hirose M,Ito N

    更新日期:1992-01-01 00:00:00

  • Growth factor responses and protooncogene expression of murine mesothelial cell lines derived from asbestos-induced mesotheliomas.

    abstract::Repeated intraperitoneal injections of crocidolite asbestos fibers induced diffuse malignant mesotheliomas in mice. A series of mesothelial cell lines was isolated from mice at different stages in the development of these tumors. The cell lines isolated from mice with mesotheliomas recapitulated their growth pattern i...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339702500605

    authors: Goodglick LA,Vaslet CA,Messier NJ,Kane AB

    更新日期:1997-11-01 00:00:00

  • Recombinant human interleukin-3 induces extramedullary hematopoiesis at subcutaneous injection sites in cynomolgus monkeys.

    abstract::Parenteral administration of recombinant hematopoietic growth factors has been sporadically associated with cutaneous complications, including injection site reactions in humans and nonhuman primates. In this study, subcutaneous injection sites were evaluated from 12 cynomolgus monkeys administered a recombinant human...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339602400401

    authors: Khan KN,Kats AA,Fouant MM,Snook SS,Mckearn JP,Alden CL,Smith PF

    更新日期:1996-07-01 00:00:00

  • Interruption of thrombosis and hemostasis by anti-platelet agents.

    abstract::Blood platelets play a fundamental role in hemostasis and thrombosis. The physiological role of platelets is to preserve the integrity of the cardiovascular system such that upon injury platelets are activated and serve to interrupt a potentially deleterious situation (i.e., hemorrhage). However, platelets are also in...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339302100210

    authors: Shebuski RJ

    更新日期:1993-01-01 00:00:00

  • Twenty-six-Week carcinogenicity study of chloroform in CB6F1 rasH2-transgenic mice.

    abstract::The carcinogenic potential of chloroform was evaluated in a short-term carcinogenicity testing system using CB6F1 rasH2-Tg (rasH2-Tg) mice. Chloroform was administered to rasH2-Tg males at doses of 28, 90, or 140 mg/kg and rasH2-Tg females at 24, 90, or 240 mg/kg by oral gavage for 26 weeks. Wild-type (non-Tg) male an...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1080/01926230252929909

    authors: Sehata S,Maejima T,Watanabe M,Ogata S,Makino T,Tanaka K,Manabe S,Takaoka M

    更新日期:2002-05-01 00:00:00

  • Early stages of nodular transformation of the B6C3F1 mouse liver induced by choline deficiency.

    abstract::The B6C3F1 strain of mice is prone to develop liver nodules as animals grow older. This spontaneous tumor development is enhanced by dietary lipotrope deficiency. The present studies were performed to evaluate the liver of the B6C3F1 mice in early periods of lipotrope deficiency and before the nodules appear. Mice wer...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262338501300103

    authors: de Camargo JL,Punyarit P,Newberne PM

    更新日期:1985-01-01 00:00:00

  • Generalized cellular hypertrophy is induced by a dual-acting PPAR agonist in rat urinary bladder urothelium in vivo.

    abstract::Some developmental dual-acting PPARalpha/gamma agonists, such as ragaglitazar, have shown carcinogenic effects in the rodent urinary bladder urothelium after months-years of dosing. We examined early (precancerous) changes in the bladder urothelium of rats orally dosed with ragaglitazar, using a newly developed flow c...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1080/01926230500214657

    authors: Oleksiewicz MB,Thorup I,Nielsen HS,Andersen HV,Hegelund AC,Iversen L,Guldberg TS,Brinck PR,Sjogren I,Thinggaard UK,Jørgensen L,Jensen MB

    更新日期:2005-01-01 00:00:00

  • Spontaneous Age-Related Histopathological Changes in Microminipigs.

    abstract::Microminipigs have become an attractive animal model for toxicology and pharmacology studies and for human disease models, owing to their manageable size. Although there are numerous reports of spontaneous age-related lesions in mice, rats, dogs, and monkeys, those in minipigs are scarce. In the present study, spontan...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623319861350

    authors: Kangawa A,Nishimura T,Nishimura T,Otake M,Enya S,Yoshida T,Shibata M

    更新日期:2019-10-01 00:00:00

  • Histopathology of the spleen.

    abstract::The spleen contains hematopoietic and lymphoid elements, is a primary site of extramedullary hematopoiesis, and removes degenerate and aged red blood cells as well as particulate materials and circulating bacteria from the blood supply. Lesions of this important component of the immune system may center on the red pul...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1080/01926230600867750

    authors: Suttie AW

    更新日期:2006-01-01 00:00:00

  • Occult cardiotoxicity--toxic effects on cardiac ischemic tolerance.

    abstract::The outcome of cardiac ischemic events depends not only on the extent and duration of the ischemic stimulus but also on the myocardial intrinsic tolerance to ischemic injury. Cardiac ischemic tolerance reflects myocardial functional reserves that are not always used when the tissue is appropriately oxygenated. Ischemi...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1177/0192623309339503

    authors: Golomb E,Nyska A,Schwalb H

    更新日期:2009-08-01 00:00:00

  • Pathophysiological effects of chronic toxicity with synthetic pyrethroid, organophosphate and chlorinated pesticides on bone health of broiler chicks.

    abstract::This experiment evaluated effects following chronic toxicity with 20 ppm fenvalerate (synthetic pyrethroid), 2 ppm monocrotophos (organophosphate) and 2 ppm endosulfan (chlorinated hydrocarbon) on bone health of broiler chicks. A total of 120 chicks were divided equally into 4 groups and were fed poultry mash without ...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1080/01926230490431745

    authors: Garg UK,Pal AK,Jha GJ,Jadhao SB

    更新日期:2004-05-01 00:00:00

  • Differentiation Patterns of Uterine Carcinomas and Precursor Lesions Induced by Neonatal Estrogen Exposure in Mice.

    abstract::Developmental exposure to estrogenic chemicals is an established risk factor for cancer of the female reproductive tract. This increase in risk has been associated with disruption of normal patterns of cellular differentiation during critical stages of morphogenesis. The goal of this study was to document uterine epit...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623318779326

    authors: Suen AA,Jefferson WN,Williams CJ,Wood CE

    更新日期:2018-07-01 00:00:00

  • Long-term parenteral administration of 2-hydroxypropyl-β-cyclodextrin causes bone loss.

    abstract::Cyclodextrins are oligosaccharides which are used in the pharmaceutical industry and research as vehicles for application of apolar substances such as steroids. The aim of this study was to examine the long-term effects of parenteral administration of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on bone. Sham-operated (SH...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623312441405

    authors: Kantner I,Erben RG

    更新日期:2012-07-01 00:00:00

  • In situ phosphorylation of Akt and ERK1/2 in rat mammary gland, colon, and liver following treatment with human insulin and IGF-1.

    abstract::High doses of insulin and the insulin analog AspB10 have been reported to increase mammary tumor incidence in female rats likely via receptor-mediated mechanisms, possibly involving enhanced IGF-1 receptor activation. However, insulin and IGF-1 receptor functionality and intracellular signaling in the rat mammary glan...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623311406936

    authors: Hvid H,Fels JJ,Kirk RK,Thorup I,Jensen HE,Hansen BF,Oleksiewicz MB

    更新日期:2011-06-01 00:00:00

  • Dose-response relationship of diethylnitrosamine-initiated tumors in neonatal balb/c mice: effect of phenobarbital promotion.

    abstract::The dose-response of diethylnitrosamine (DENA) initiation of hepatocarcinogenesis was determined in infant Balb/c male mice with and without subsequent phenobarbital treatment. Male Balb/c mice received a single intraperitoneal injection of DENA (0, 2.5, 10.0, 25.0 or 50.0 micrograms/gbw) in saline on day 15 of age. N...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262338801600310

    authors: Klaunig JE,Pereira MA,Ruch RJ,Weghorst CM

    更新日期:1988-01-01 00:00:00

  • Carcinogenicity testing of antitumor agents.

    abstract::Carcinogenicity testing of antitumor agents in animal bioassays has been proposed because of the potential for carcinogenicity of this class of agents and the expectation that such testing may indicate prospectively the target organs of any related human oncogenesis. The literature reveals the anticipated confirmation...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262338501300305

    authors: Hottendorf GH

    更新日期:1985-01-01 00:00:00

  • A 13-week subchronic intravaginal toxicity study of the novel broad-spectrum anti-HIV and spermicidal agent, N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea (PHI-346) in mice.

    abstract::The nonnucleoside inhibitor (NNI) of HIV-1 reverse transcriptase, PHI-346 (N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea), is a dual-function spermicidal agent with potent anti-HIV activity against drug-sensitive as well as drug-resistant HIV-1 strains with genotypic and phenotypic NNI resistance. PHI-3...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1080/01926230290168551

    authors: D'Cruz OJ,Waurzyniak B,Uckun FM

    更新日期:2002-11-01 00:00:00

  • Brainstem axonal degeneration in mice with deletion of selenoprotein p.

    abstract::Selenoprotein P is an abundant extracellular protein that is expressed in liver, brain, and other tissues. Studies in mice with the selenoprotein P gene deleted (Sepp-/- mice) have implicated the protein in maintaining brain selenium. Sepp-/- mice fed a normal or low selenium diet develop severe motor impairment and d...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1080/01926230500243045

    authors: Valentine WM,Hill KE,Austin LM,Valentine HL,Goldowitz D,Burk RF

    更新日期:2005-01-01 00:00:00

  • p27(Kip1) (Cdkn1b)-deficient mice are susceptible to chemical carcinogenesis and may be a useful model for carcinogen screening.

    abstract::The two-year rodent bioassay is one of several tests that are widely used by governmental regulatory agencies as well as pharmaceutical and chemical companies to determine the carcinogenic potential of chemicals or environmental agents where human exposure is anticipated. That this assay has remained relatively unchan...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1080/01926230390201273

    authors: Payne SR,Kemp CJ

    更新日期:2003-07-01 00:00:00

  • Toxicosis associated with dual oral exposure of rats to lead and trichloroethylene.

    abstract::To determine if additive or synergistic toxic effects would occur, adult male rats were exposed orally to lead carbonate (2,000 mg/kg) for 9 days before trichloroethylene (TCE), 2,000 mg/kg, was given concurrently for an additional 7 days. Comparisons were made with groups of vehicle-treated rats and rats given only l...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1080/01926230152499809

    authors: Nunes J,Ehrich M,Robertson J

    更新日期:2001-07-01 00:00:00

  • Whole mount enzyme histochemistry as a rapid screen at necropsy for expression of beta-galactosidase (LacZ)-bearing transgenes: considerations for separating specific LacZ activity from nonspecific (endogenous) galactosidase activity.

    abstract::Whole mount enzyme histochemistry to localize lacZ-bearing transgenes (lacZ-WMH) also detects endogenous beta-galactosidases. The experiments reported here evaluated lacZ-WMH as a potential tool for transgene expression analysis during high-throughput rodent necropsies. A lacZ-WMH survey of organs from adult, wild-typ...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623307312693

    authors: Bolon B

    更新日期:2008-02-01 00:00:00

  • Characterization of Spontaneous Vascular Findings in the Papillary Muscles of Beagle Dogs.

    abstract::Standard histology trimming practices for toxicity studies in dogs include preparation of a section of the papillary muscle associated with the left ventricular free wall-the anteriolateral or anterior muscle. In contrast, the posteromedial or posterior papillary muscle, associated with the interventricular septum, is...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623320963020

    authors: Kohnken R,Weber A

    更新日期:2020-10-01 00:00:00

  • TCDD: an environmental immunotoxicant reveals a novel pathway of immunoregulation--a 30-year odyssey.

    abstract::I was honored to be the keynote speaker at the 30th Annual Society of Toxicologic Pathology Symposium "Toxicologic Pathology and the Immune System." I had the opportunity to reminisce about events in the 1970s that set the stage for the birth and subsequent growth of the field of immunotoxicology and to summarize my r...

    journal_title:Toxicologic pathology

    pub_type: 历史文章

    doi:10.1177/0192623311427710

    authors: Kerkvliet NI

    更新日期:2012-01-01 00:00:00