Toxicologic Pathology of the Eye: Histologic Preparation and Alterations of the Anterior Segment

Schafer, Kenneth A.; Render, James A.

doi:10.1007/978-1-62703-164-6_5

Cited by 12 publications

(25 citation statements)

References 176 publications

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“…It could provide valuable information on blood vessel growth, detect neovascularization or choroidal lesions, and allow for longitudinal assessment of ocular vascular diseases. In addition, better in vivo imaging of ocular structures in general might further improve correlation with histopathology (Schafer and Render 2013).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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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 Gö ttingen 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-a, 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, a-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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…To achieve accurate histopathological evaluation, quality of the his-tological slides has to be critically taken into account. In this regard, there are several papers that describe the technical considerations in detail (Schafer and Render, 2013a;Onodera et al, 2015;Shibuya et al, 2015).…”

Section: Histopathological Examinations For the Eyes And Ocular Accesmentioning

confidence: 99%

“…If the test article has pharmacological action of vasodilation, hyperemia will be transient and not accompanied by histopathological changes. If hyperemia is a sequela of tissue injury, edema and histopathological inflammatory changes will be present (Schafer and Render, 2013a).…”

Section: Cornea Conjunctive and Eyelidsmentioning

confidence: 99%

“…Decreases in lacrimal secretion result in keratoconjunctivitis sicca (Schafer and Render, 2013a). Several eye drop drugs are known to induce dysfunction of the lacrimal systems (Fraunfelder et al, 2008b).…”

Section: Cornea Conjunctive and Eyelidsmentioning

confidence: 99%

“…IOP is influenced by primary pharmacological actions (i.e., glaucoma therapeutic agent), off-target pharmacological effects, malfunction or damage of tissues following inflammatory changes (Schafer and Render, 2013a). An elevation of IOP, when prolonged, may cause symptoms of glaucoma, followed by functional ocular damage, even of vision.…”

Section: Uveamentioning

confidence: 99%

See 2 more Smart Citations

Ocular instillation toxicity study: current status and points to consider on study design and evaluation

Kurata

Atsumi

Yamagiwa

et al. 2016

Fundam. Toxicol. Sci.

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Ocular instillation toxicity studies (OITSs) are one of general toxicity studies. Yet, OITSs have a unique characteristic that the test article is directly administered as eye drops to the target organ. Compared with general toxicity studies aiming systemic exposure, the study design of OITSs is somewhat distinctive in selecting test species, dosing formulation, administration volume/frequency and ocular examinations. After the administration of eye drops, the exposure level is high in the ocular surface, whereas the bioavailability in the eye balls, especially in the posterior segment, is low. In contrast to the general toxicity studies aiming systemic exposure, the absolute systemic exposure level in OITSs is generally low, while the systemic bioavailability is relatively high. These pharmacokinetic features determine the profiles of local and systemic toxicities in OITSs. Systemic toxicities are more often found in animals of relatively small body size, and are in most cases related with pharmacological actions. Current progress in ophthalmologic imaging technologies enables advanced safety evaluation using imaging biomarkers. Bioanalysis detecting drug levels present in blood in trace amount leads to a detailed safety assessment of systemic toxicity and yields accurate safety margins. Recognizing the peculiar characteristics of OITSs, toxicologists need to propose an appropriate study design and strategy of safety evaluation. Further discussion may be awaited on rationales for testing both sexes, and for conducting separated toxicity studies to evaluate systemic toxicity. This mini-review provides insight regarding current status and points to consider of OITSs.

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Presumed congenital nictitating membrane dysplasia in a Japanese white rabbit

Masatsugu

Atsumi

Yamagiwa

et al. 2022

Veterinary Medicine & Sci

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Objective:The present report characterises a spontaneous nictitating membrane abnormality in a Japanese white rabbit. Animal studied:The animal was a male Japanese white rabbit (Oryctolagus cuniculus, Kbs:JW, 10 weeks old at the time of purchase) that had not received any treatment. A morphological abnormality of the nictitating membrane in the animal's right eye was detected.Procedures: Ophthalmological examinations, including slit-lamp biomicroscopy, corneal and conjunctival staining with fluorescein and lissamine green, fundoscopy, blinking rate measurement, Schirmer's tear test, and tonometry were performed. The animal was euthanised at 15 weeks of age, and histopathological examinations of the abnormal nictitating membrane, palpebral conjunctiva, eyelid and eyeball were performed. Results:The tip of the nictitating membrane adhered to the palpebral conjunctiva of the medial canthus. The eye and periocular tissues showed no abnormalities in the ophthalmological examinations, except for the structure of the nictitating membrane.Histopathological examination revealed that the adhered site of the nictitating membrane and the palpebral conjunctiva consisted of dense fibrous connective tissue that was consecutive to the conjunctiva adjacent to the eyelid margin and lamina propria of the nictitating membrane. The fibrous connective tissue was covered with stratified squamous epithelium. Conclusion:Based on these results, we diagnosed this abnormal finding as congenital nictitating membrane dysplasia. This paper is the first case report describing a congenital structural abnormality of the nictitating membrane in a Japanese white rabbit.

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Toxicologic Pathology of the Eye: Histologic Preparation and Alterations of the Anterior Segment

Cited by 12 publications

References 176 publications

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

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

Ocular instillation toxicity study: current status and points to consider on study design and evaluation

Presumed congenital nictitating membrane dysplasia in a Japanese white rabbit

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