Light Microscopic Comparison of Surfactant-Induced Eye Irritation in Rabbits and Rats at Three Hours and Recovery/Day 35*<sup>1</sup>

Maurer, James K.; Parker, Ronald D.

doi:10.1177/019262339602400403

Cited by 39 publications

(53 citation statements)

References 32 publications

(26 reference statements)

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“…These results are consistent with those reported for rabbits and rats receiving 10 [LI of a slightly irritating anionic surfactant in which the median days to recovery were 3 and 1 in the rabbit and rat, respectively (24). Although in the rat the mean macroscopic scores increased, this increase was due to an atypically severe response in I rat.…”

Section: Figsupporting

confidence: 91%

“…This is consistent with data from previous rabbit studies indicating that this surfactant causes severe ocular irritation (24). Using in vivo CM, changes were detected throughout the anterior cornea and included loss of corneal epithelium, the deposition of small, highly reflective particles in the corneal stroma of both the rat and rabbit, and loss or damage to the corneal endothelium in the rat.…”

Section: Figsupporting

confidence: 90%

“…In the rabbit, the macroscopic and slit-lamp scores for the treated eyes peaked at 3 hr after dosing and tended to return to normal by day 3. The ranges in observed responses to the anionic and cationic surfactants were similar to those reported in the companion study (24).…”

Section: Introductionsupporting

confidence: 74%

“…Alternative in vitro tests have been broadly characterized into 2 types based on use; screens, and replacements (13,14,24). Although there are numerous screening tests available, at present there are no clearly recognized in vitro replacements for accessing ocular irritation (6,11).…”

Section: Introductionmentioning

confidence: 99%

“…The LVET was used, in preference to the Draize test, because it is less stressful to rabbits and is more predictive of human ocular irritancy potential than the standard Draize procedure (9). Rats and rabbits were used because previous studies have suggested that the rat may be an appropriate alternative species to rabbits for studying mechanisms of eye irritation (24). Surfactants studied were selected based on previous rabbit eye irritation data indicating the anionic surfactant caused slight irritation and the cationic surfactant caused severe irritation.…”

Section: Introductionmentioning

confidence: 99%

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Application of In Vivo Confocal Microscopy to the Understanding of Surfactant-Induced Ocular Irritation*^{Oryzias latipes}

et al. 1996

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The purpose of this study was to assess the ability of in vivo confocal microscopy (CM) to provide noninvasively derived histopathologic correlates of surfactant-induced eye irritation from which specific pathologic mechanisms can be identified and later evaluated in alternative in vitro models. Rats and rabbits, divided into groups of 5, received 10 μl of an anionic or cationic surfactant in one eye with the other eye used as a control. At specified times, eyes were examined and scored for ocular irritancy using a penlight and slit-lamp. Subsequently, corneas were evaluated by in vivo CM to evaluate epithelial layer thickness and surface epithelial cell area, corneal thickness, depth of necrosis, inflammation, fibrosis, and endothelial injury. At 3 hr, the anionic surfactant produced slight irritation with peak scores of 12.4 and 8.0 out of a possible 110 in the rats and rabbits, respectively. In vivo CM revealed changes limited to the corneal epithelium that decreased in thickness to 78% in rats and 81% in rabbits at 3 hr. This decrease in the thickness correlated with a significant decrease in surface epithelial cell area from 2,061 & p l u s m n ; 395 μm 2 to 567 & p l u s m n ; 330 μm 2 in the rats and 1,523 ± 185 μm 2 to 934 ± 71 μm 2 in the rabbits (p < 0.005 and 0.005, respectively). The cationic surfactant produced severe irritation in both the rats and rabbits with peak scores of 85.4 and 80.2 occurring at day 2, respectively. In vivo CM in the rats showed complete loss of corneal epithelium, lysis of keratocytes, and loss of corneal endothelium. In the rabbits, injury appeared limited to the anterior cornea with complete loss of epithelium and loss of keratocytes extending to 52% of the corneal thickness. These findings establish the application of noninvasive, in vivo CM to qualitatively and quantitatively characterize the pathobiology of ocular irritation in situ. This information will be important in the development and evaluation of mechanistically based in vitro alternatives for ocular irritancy testing.

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Section: Figsupporting

confidence: 91%

Section: Figsupporting

confidence: 90%

Section: Introductionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Application of In Vivo Confocal Microscopy to the Understanding of Surfactant-Induced Ocular Irritation*^{Oryzias latipes}

et al. 1996

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Ricinoleic acid-based biopolymers

Teomim

Nyska

Domb

1999

J. Biomed. Mater. Res.

123

102

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Polyanhydrides synthesized from pure ricinoleic acid half-esters with maleic and succinic anhydrides possess desired physicochemical and mechanical properties for use as drug carriers. Ricinoleic acid maleate or succinate diacid half-esters were prepared from the reaction of crude ricinoleic acid (85% content) with succinic or maleic anhydride. The pure diacid monomers were obtained by chromatography purification through silica gel using petroleum ether/ethyl acetate/acetic acid (80/30/1 v/v/v) mixture as eluent. The pure diacid monomers (>99%) were polymerized by melt condensation to yield film-forming polymers with molecular weights exceeding 40,000 with a polydispersity of 2. Extensive biocompatibility study demonstrated their toxicological inertness and biodegradability. Their rate of elimination from rats in the course of about 4-6 weeks was faster than that found for similar fatty acid-based polyanhydrides previously tested. In vitro studies showed that these polymers underwent rapid hydrolytic degradation in 10 days. Methotrexate release from the polymers was not affected by the initial polymer molecular weight in the range of 10,000-35,000. The in vitro drug release correlated with the degradation of the polymers. The fatty acid ester monomers were further degraded to its counterparts, ricinoleic acid and succinic or maleic acid.

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Ricinoleic acid-based biopolymers

Teomim¹,

Nyska²,

Domb³

1999

J. Biomed. Mater. Res.

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Polyanhydrides synthesized from pure ricinoleic acid half-esters with maleic and succinic anhydrides possess desired physicochemical and mechanical properties for use as drug carriers. Ricinoleic acid maleate or succinate diacid half-esters were prepared from the reaction of crude ricinoleic acid (85% content) with succinic or maleic anhydride. The pure diacid monomers were obtained by chromatography purification through silica gel using petroleum ether/ ethyl acetate/acetic acid (80/30/1 v/v/v) mixture as eluent. The pure diacid monomers (>99%) were polymerized by melt condensation to yield film-forming polymers with molecular weights exceeding 40,000 with a polydispersity of 2. Extensive biocompatibility study demonstrated their toxicological inertness and biodegradability. Their rate of elimination from rats in the course of about 4-6 weeks was faster than that found for similar fatty acid-based polyanhydrides previously tested. In vitro studies showed that these polymers underwent rapid hydrolytic degradation in 10 days. Methotrexate release from the polymers was not affected by the initial polymer molecular weight in the range of 10,000-35,000. The in vitro drug release correlated with the degradation of the polymers. The fatty acid ester monomers were further degraded to its counterparts, ricinoleic acid and succinic or maleic acid.

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Light Microscopic Comparison of Surfactant-Induced Eye Irritation in Rabbits and Rats at Three Hours and Recovery/Day 35*¹

Cited by 39 publications

References 32 publications

Application of In Vivo Confocal Microscopy to the Understanding of Surfactant-Induced Ocular Irritation*^{Oryzias latipes}

Application of In Vivo Confocal Microscopy to the Understanding of Surfactant-Induced Ocular Irritation*^{Oryzias latipes}

Ricinoleic acid-based biopolymers

Ricinoleic acid-based biopolymers

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Light Microscopic Comparison of Surfactant-Induced Eye Irritation in Rabbits and Rats at Three Hours and Recovery/Day 35*1

Cited by 39 publications

References 32 publications

Application of In Vivo Confocal Microscopy to the Understanding of Surfactant-Induced Ocular Irritation*Oryzias latipes

Application of In Vivo Confocal Microscopy to the Understanding of Surfactant-Induced Ocular Irritation*Oryzias latipes

Ricinoleic acid-based biopolymers

Ricinoleic acid-based biopolymers

Contact Info

Product

Resources

About

Light Microscopic Comparison of Surfactant-Induced Eye Irritation in Rabbits and Rats at Three Hours and Recovery/Day 35*¹

Application of In Vivo Confocal Microscopy to the Understanding of Surfactant-Induced Ocular Irritation*^{Oryzias latipes}

Application of In Vivo Confocal Microscopy to the Understanding of Surfactant-Induced Ocular Irritation*^{Oryzias latipes}