The effects of 3% diquafosol sodium application on the tear functions and ocular surface of the Cu,Zn-superoxide dismutase-1 (Sod1)-knockout mice

Takashi Kojima, Murat Dogru, Osama M. Ibrahim, Taeko Nagata, Kazunari Higa, Takahiko Shimizu, Takuji Shirasawa, Yoshiyuki Satake, Seika Shimazaki, Jun Shimazaki, Kazuo Tsubota

研究成果: Article

18 引用 (Scopus)

抄録

To investigate the role of a water and mucin secretagogue (3% diquafosol sodium eye drops) on the tear function and conjunctival ocular surface changes in Sod1-/- in comparison to the wild-type (WT) mice. Methods: Fourteen eyes of 7 Sod1-/- male mice with C57BL/background and 14 eyes of 7 C57BL6 strain wild-type male mice were examined at 40 weeks in this study. All mice had application of 3% diquafosol ophthalmic solution six times a day for 2 weeks. Tear film stability and corneal epithelial damage was evaluated by fluorescein and Rose Bengal stainings. Anterior segment photography was performed before and after eye drop instillations. Aqueous tear quantity was measured with phenol red-impregnated cotton threads without anesthesia. Animals were sacrificed at 42 weeks after diquafosol treatment and the whole globe specimens were subjected to periodic acid Schiff staining. Goblet cell density was quantified by J Image software. Quantitative real-time PCR for conjunctival muc 5AC messenger RNA expression was also performed. Results: Sod1-/- mice had significantly higher fluorescein staining scores compared to the WT mice before eye drop instillation. The mean tear film breakup time, Rose Bengal staining scores, and muc5 messenger RNA expression improved significantly with diquafosol treatment in both the WT and the knockout mice. The mean fluorescein staining score and aqueous tear quantity significantly improved in the Sod1-/- mice with treatment. A notable and consistent increase in goblet cells and decrease in inflammatory cell infiltrates could be confirmed in all specimens after 2 weeks of diquafosol eye drop application. Conclusions: Three percent diquafosol ophthalmic solution appears to be effective in the treatment of ocular surface disease in this age-related dry eye disease mouse model.

元の言語English
ページ(範囲)929-938
ページ数10
ジャーナルMolecular Vision
20
出版物ステータスPublished - 2014 6 28

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Tears
Ophthalmic Solutions
Knockout Mice
Sodium
Staining and Labeling
Fluorescein
Rose Bengal
Goblet Cells
Eye Diseases
Mucin-3
Phenolsulfonphthalein
Messenger RNA
Periodic Acid
Photography
diquafosol
Superoxide Dismutase-1
Inbred C57BL Mouse
Real-Time Polymerase Chain Reaction
Software
Anesthesia

ASJC Scopus subject areas

  • Ophthalmology

これを引用

The effects of 3% diquafosol sodium application on the tear functions and ocular surface of the Cu,Zn-superoxide dismutase-1 (Sod1)-knockout mice. / Kojima, Takashi; Dogru, Murat; Ibrahim, Osama M.; Nagata, Taeko; Higa, Kazunari; Shimizu, Takahiko; Shirasawa, Takuji; Satake, Yoshiyuki; Shimazaki, Seika; Shimazaki, Jun; Tsubota, Kazuo.

:: Molecular Vision, 巻 20, 28.06.2014, p. 929-938.

研究成果: Article

Kojima, T, Dogru, M, Ibrahim, OM, Nagata, T, Higa, K, Shimizu, T, Shirasawa, T, Satake, Y, Shimazaki, S, Shimazaki, J & Tsubota, K 2014, 'The effects of 3% diquafosol sodium application on the tear functions and ocular surface of the Cu,Zn-superoxide dismutase-1 (Sod1)-knockout mice', Molecular Vision, 巻. 20, pp. 929-938.
Kojima, Takashi ; Dogru, Murat ; Ibrahim, Osama M. ; Nagata, Taeko ; Higa, Kazunari ; Shimizu, Takahiko ; Shirasawa, Takuji ; Satake, Yoshiyuki ; Shimazaki, Seika ; Shimazaki, Jun ; Tsubota, Kazuo. / The effects of 3% diquafosol sodium application on the tear functions and ocular surface of the Cu,Zn-superoxide dismutase-1 (Sod1)-knockout mice. :: Molecular Vision. 2014 ; 巻 20. pp. 929-938.
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abstract = "To investigate the role of a water and mucin secretagogue (3{\%} diquafosol sodium eye drops) on the tear function and conjunctival ocular surface changes in Sod1-/- in comparison to the wild-type (WT) mice. Methods: Fourteen eyes of 7 Sod1-/- male mice with C57BL/background and 14 eyes of 7 C57BL6 strain wild-type male mice were examined at 40 weeks in this study. All mice had application of 3{\%} diquafosol ophthalmic solution six times a day for 2 weeks. Tear film stability and corneal epithelial damage was evaluated by fluorescein and Rose Bengal stainings. Anterior segment photography was performed before and after eye drop instillations. Aqueous tear quantity was measured with phenol red-impregnated cotton threads without anesthesia. Animals were sacrificed at 42 weeks after diquafosol treatment and the whole globe specimens were subjected to periodic acid Schiff staining. Goblet cell density was quantified by J Image software. Quantitative real-time PCR for conjunctival muc 5AC messenger RNA expression was also performed. Results: Sod1-/- mice had significantly higher fluorescein staining scores compared to the WT mice before eye drop instillation. The mean tear film breakup time, Rose Bengal staining scores, and muc5 messenger RNA expression improved significantly with diquafosol treatment in both the WT and the knockout mice. The mean fluorescein staining score and aqueous tear quantity significantly improved in the Sod1-/- mice with treatment. A notable and consistent increase in goblet cells and decrease in inflammatory cell infiltrates could be confirmed in all specimens after 2 weeks of diquafosol eye drop application. Conclusions: Three percent diquafosol ophthalmic solution appears to be effective in the treatment of ocular surface disease in this age-related dry eye disease mouse model.",
author = "Takashi Kojima and Murat Dogru and Ibrahim, {Osama M.} and Taeko Nagata and Kazunari Higa and Takahiko Shimizu and Takuji Shirasawa and Yoshiyuki Satake and Seika Shimazaki and Jun Shimazaki and Kazuo Tsubota",
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T1 - The effects of 3% diquafosol sodium application on the tear functions and ocular surface of the Cu,Zn-superoxide dismutase-1 (Sod1)-knockout mice

AU - Kojima, Takashi

AU - Dogru, Murat

AU - Ibrahim, Osama M.

AU - Nagata, Taeko

AU - Higa, Kazunari

AU - Shimizu, Takahiko

AU - Shirasawa, Takuji

AU - Satake, Yoshiyuki

AU - Shimazaki, Seika

AU - Shimazaki, Jun

AU - Tsubota, Kazuo

PY - 2014/6/28

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N2 - To investigate the role of a water and mucin secretagogue (3% diquafosol sodium eye drops) on the tear function and conjunctival ocular surface changes in Sod1-/- in comparison to the wild-type (WT) mice. Methods: Fourteen eyes of 7 Sod1-/- male mice with C57BL/background and 14 eyes of 7 C57BL6 strain wild-type male mice were examined at 40 weeks in this study. All mice had application of 3% diquafosol ophthalmic solution six times a day for 2 weeks. Tear film stability and corneal epithelial damage was evaluated by fluorescein and Rose Bengal stainings. Anterior segment photography was performed before and after eye drop instillations. Aqueous tear quantity was measured with phenol red-impregnated cotton threads without anesthesia. Animals were sacrificed at 42 weeks after diquafosol treatment and the whole globe specimens were subjected to periodic acid Schiff staining. Goblet cell density was quantified by J Image software. Quantitative real-time PCR for conjunctival muc 5AC messenger RNA expression was also performed. Results: Sod1-/- mice had significantly higher fluorescein staining scores compared to the WT mice before eye drop instillation. The mean tear film breakup time, Rose Bengal staining scores, and muc5 messenger RNA expression improved significantly with diquafosol treatment in both the WT and the knockout mice. The mean fluorescein staining score and aqueous tear quantity significantly improved in the Sod1-/- mice with treatment. A notable and consistent increase in goblet cells and decrease in inflammatory cell infiltrates could be confirmed in all specimens after 2 weeks of diquafosol eye drop application. Conclusions: Three percent diquafosol ophthalmic solution appears to be effective in the treatment of ocular surface disease in this age-related dry eye disease mouse model.

AB - To investigate the role of a water and mucin secretagogue (3% diquafosol sodium eye drops) on the tear function and conjunctival ocular surface changes in Sod1-/- in comparison to the wild-type (WT) mice. Methods: Fourteen eyes of 7 Sod1-/- male mice with C57BL/background and 14 eyes of 7 C57BL6 strain wild-type male mice were examined at 40 weeks in this study. All mice had application of 3% diquafosol ophthalmic solution six times a day for 2 weeks. Tear film stability and corneal epithelial damage was evaluated by fluorescein and Rose Bengal stainings. Anterior segment photography was performed before and after eye drop instillations. Aqueous tear quantity was measured with phenol red-impregnated cotton threads without anesthesia. Animals were sacrificed at 42 weeks after diquafosol treatment and the whole globe specimens were subjected to periodic acid Schiff staining. Goblet cell density was quantified by J Image software. Quantitative real-time PCR for conjunctival muc 5AC messenger RNA expression was also performed. Results: Sod1-/- mice had significantly higher fluorescein staining scores compared to the WT mice before eye drop instillation. The mean tear film breakup time, Rose Bengal staining scores, and muc5 messenger RNA expression improved significantly with diquafosol treatment in both the WT and the knockout mice. The mean fluorescein staining score and aqueous tear quantity significantly improved in the Sod1-/- mice with treatment. A notable and consistent increase in goblet cells and decrease in inflammatory cell infiltrates could be confirmed in all specimens after 2 weeks of diquafosol eye drop application. Conclusions: Three percent diquafosol ophthalmic solution appears to be effective in the treatment of ocular surface disease in this age-related dry eye disease mouse model.

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