Citation:Moon CH,Lee JY,Kim ES,Park JH,Kim SY,Kim JY,Tchah H.In vivo biodistribution of topical low molecular weight heparin-taurocholate in a neovascularized mouse cornea.Int J Ophthalmol 2018;11(9):1435-1439,doi:10.18240/ijo.2018.09.01
In vivo biodistribution of topical low molecular weight heparin-taurocholate in a neovascularized mouse cornea
Received:February 26, 2017  Revised:July 05, 2018
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DOI:10.18240/ijo.2018.09.01
Key Words:corneal neovascularization; in vivo optical imaging; low-molecular weight heparin; ocular biodistribution
Fund Project:Supported by a grant (No.2016-7026) from the Asan Institute for Life Science, Seoul, Republic of Korea.
                    
AuthorInstitution
Chan Hee Moon Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
Ji Yun Lee Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
Eun Soon Kim Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
Jin Hyoung Park Research Institute for Biomacromolecules, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea
Sang-Yeob Kim Department of Convergence Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea
Jae Yong Kim Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
Hungwon Tchah Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
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Abstract:
      AIM: To investigate the ocular biodistribution and clearance of topically administered 7-taurocholic acid conjugated low-molecular weight heparin (LHT7) in a neovascularized mouse cornea using an in vivo optical imaging system.

    METHODS: A total of 10 eyes of 6 to 8-week-old BALB/c mice were analyzed. Corneal neovascularization (CoNV) was induced in the inferior cornea (IC) of each animal by penetrating the stroma with two interrupted sutures. The development of CoNV was verified after one week and the area of each neovascularized region was measured. A near-infrared fluorescent probe of 20 μmol/L Cy5.5 labeled LHT7 (LHT7-Cy5.5) in 0.02 mL solution was topically instilled onto the cornea in the experimental group (n=5). Free-Cy5.5 of 20 μmol/L in 0.02 mL was instilled in the control group (n=5). In vivo optical images were obtained before instillation and 5min, 2, 4, and 6h after instillation. The intensities were separately measured at the superior cornea (SC) and the IC.

    RESULTS: The mean CoNV areas were 1.97±0.17 mm2 and 1.92±0.96 mm2 in the experimental and control groups, respectively (P=0.832). The SC remained normal in all 10 subject animals. The IC intensity of the LHT7-Cy5.5 was greater than the SC intensity at 5min (P=0.038), 2h (P=0.041), and 4h (P=0.041) after application. The IC intensity fell to less than half of its initial value (42.9%±8.6%) at 6h in the experimental group. In the control mice, here were no significant differences in the free-Cy5.5 intensity between the IC and SC.

    CONCLUSION: Topically administered LHT7 shows a high biodistribution in CoNV areas for 4h and should be reapplied accordingly to maintain its effects. In vivo optical imaging can be a useful tool for evaluating the ocular biodistribution of a drug in an animal model.

PMC FullText Html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133895/
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