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Ken-ichi Hosoya - One of the best experts on this subject based on the ideXlab platform.

  • Recent advances in drug and nutrient transport across the Blood-Retinal Barrier.
    Expert opinion on drug metabolism & toxicology, 2018
    Co-Authors: Yoshiyuki Kubo, Shin-ichi Akanuma, Ken-ichi Hosoya
    Abstract:

    ABSTRACTIntroduction: The Blood-Retinal Barrier (BRB) is the Barrier separating the blood and neural retina, and transport systems for low-weight molecules at the BRB are expected to be useful for ...

  • Localization of organic anion transporting polypeptide (Oatp) 1a4 and Oatp1c1 at the rat Blood-Retinal Barrier.
    Fluids and Barriers of the CNS, 2013
    Co-Authors: Shin-ichi Akanuma, Shiro Hirose, Masanori Tachikawa, Ken-ichi Hosoya
    Abstract:

    Background Organic anion transporting polypeptide (Oatp) transporters at the blood–brain Barrier (BBB) and the Blood-Retinal Barrier (BRB), which consists of retinal capillary endothelial cells and retinal pigment epithelial cells, are major determinants of the control of anionic drugs into the brain and retina. Although Oatp1a4 (Slco1a4) and Oatp1c1 (Slco1c1) are known to be expressed in the abluminal and luminal membrane of the rat BBB and Oatp1a4 is known to be expressed at the BRB, the expression and localization of Oatp1c1 at the BRB and subcellular localization of Oatp1a4 at the BRB have received little attention. Therefore, the purpose of present study was to determine the cellular and subcellular localization of Oatp1a4 and 1c1 at the BRB.

  • The Inner Blood-Retinal Barrier
    Advances in experimental medicine and biology, 2013
    Co-Authors: Ken-ichi Hosoya, Masanori Tachikawa
    Abstract:

    The inner Blood-Retinal Barrier (inner BRB) is created by complex tight junctions of retinal capillary endothelial cells. Although this Barrier prevents the free diffusion of substances between the circulating blood and the neural retina, the inner BRB efficiently supplies nutrients to the retina and removes endobiotics and xenobiotics from the retina to maintain a constant milieu in the neural retina. We review herein the molecular structure and transport mechanism at the inner BRB.

  • Involvement of a Novel Organic Cation Transporter in Verapamil Transport Across the Inner Blood-Retinal Barrier
    Pharmaceutical research, 2012
    Co-Authors: Yoshiyuki Kubo, Shin-ichi Akanuma, Masanori Tachikawa, Yusuke Kusagawa, Ken-ichi Hosoya
    Abstract:

    Purpose To clarify the transport and inhibition characteristics involved in verapamil transport across the inner Blood-Retinal Barrier (inner BRB).

  • Inner Blood-Retinal Barrier mediates l-isomer-predominant transport of serine.
    Journal of Pharmaceutical Sciences, 2011
    Co-Authors: Masanori Tachikawa, Shin-ichi Akanuma, Tetsuya Terasaki, Masashi Okamoto, Shirou Hirose, Daisuke Yoneyama, Ken-ichi Hosoya
    Abstract:

    D-serine, a coagonist for N-methyl-D-aspartate-type glutamate receptors, which mediate visual signal transmission, is thought to be generated from L-serine via serine racemase in the retina. However, the source of L-serine and D-serine in the retina are yet to be determined. The purpose of the present study was to investigate the characteristics of the blood-to-retina transport of serine at the inner Blood-Retinal Barrier (BRB). In vivo study revealed the blood-to-retina transport of [(3) H]L-serine with an influx clearance of 49.9 μL/(min·g retina), which is greater than that of [(3) H]D-serine. This was consistent with the L-isomer-predominant uptake of serine by conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2 cells), an in vitro inner BRB model. [(3) H]L-Serine and [(3) H]D-serine uptake by TR-iBRB2 cells took place in an Na(+)-dependent and a concentration-dependent manner with Michaelis constant values of 97.5 μM and 9.63 mM, respectively. The uptake process of [(3) H]L-serine and [(3) H]D-serine was significantly inhibited by system ASC (alanine-serine-cysteine) substrates. Polymerase chain reaction analysis and immunocytochemistry revealed the expression of ASC transporters ASCT1 and ASCT2 in TR-iBRB2 cells. These results suggest that the system ASC at the inner BRB is a potent pathway for supplying serine in the form of the L-isomer from the circulating blood to the retina.

Masanori Tachikawa - One of the best experts on this subject based on the ideXlab platform.

  • Localization of organic anion transporting polypeptide (Oatp) 1a4 and Oatp1c1 at the rat Blood-Retinal Barrier.
    Fluids and Barriers of the CNS, 2013
    Co-Authors: Shin-ichi Akanuma, Shiro Hirose, Masanori Tachikawa, Ken-ichi Hosoya
    Abstract:

    Background Organic anion transporting polypeptide (Oatp) transporters at the blood–brain Barrier (BBB) and the Blood-Retinal Barrier (BRB), which consists of retinal capillary endothelial cells and retinal pigment epithelial cells, are major determinants of the control of anionic drugs into the brain and retina. Although Oatp1a4 (Slco1a4) and Oatp1c1 (Slco1c1) are known to be expressed in the abluminal and luminal membrane of the rat BBB and Oatp1a4 is known to be expressed at the BRB, the expression and localization of Oatp1c1 at the BRB and subcellular localization of Oatp1a4 at the BRB have received little attention. Therefore, the purpose of present study was to determine the cellular and subcellular localization of Oatp1a4 and 1c1 at the BRB.

  • The Inner Blood-Retinal Barrier
    Advances in experimental medicine and biology, 2013
    Co-Authors: Ken-ichi Hosoya, Masanori Tachikawa
    Abstract:

    The inner Blood-Retinal Barrier (inner BRB) is created by complex tight junctions of retinal capillary endothelial cells. Although this Barrier prevents the free diffusion of substances between the circulating blood and the neural retina, the inner BRB efficiently supplies nutrients to the retina and removes endobiotics and xenobiotics from the retina to maintain a constant milieu in the neural retina. We review herein the molecular structure and transport mechanism at the inner BRB.

  • Involvement of a Novel Organic Cation Transporter in Verapamil Transport Across the Inner Blood-Retinal Barrier
    Pharmaceutical research, 2012
    Co-Authors: Yoshiyuki Kubo, Shin-ichi Akanuma, Masanori Tachikawa, Yusuke Kusagawa, Ken-ichi Hosoya
    Abstract:

    Purpose To clarify the transport and inhibition characteristics involved in verapamil transport across the inner Blood-Retinal Barrier (inner BRB).

  • Inner Blood-Retinal Barrier mediates l-isomer-predominant transport of serine.
    Journal of Pharmaceutical Sciences, 2011
    Co-Authors: Masanori Tachikawa, Shin-ichi Akanuma, Tetsuya Terasaki, Masashi Okamoto, Shirou Hirose, Daisuke Yoneyama, Ken-ichi Hosoya
    Abstract:

    D-serine, a coagonist for N-methyl-D-aspartate-type glutamate receptors, which mediate visual signal transmission, is thought to be generated from L-serine via serine racemase in the retina. However, the source of L-serine and D-serine in the retina are yet to be determined. The purpose of the present study was to investigate the characteristics of the blood-to-retina transport of serine at the inner Blood-Retinal Barrier (BRB). In vivo study revealed the blood-to-retina transport of [(3) H]L-serine with an influx clearance of 49.9 μL/(min·g retina), which is greater than that of [(3) H]D-serine. This was consistent with the L-isomer-predominant uptake of serine by conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2 cells), an in vitro inner BRB model. [(3) H]L-Serine and [(3) H]D-serine uptake by TR-iBRB2 cells took place in an Na(+)-dependent and a concentration-dependent manner with Michaelis constant values of 97.5 μM and 9.63 mM, respectively. The uptake process of [(3) H]L-serine and [(3) H]D-serine was significantly inhibited by system ASC (alanine-serine-cysteine) substrates. Polymerase chain reaction analysis and immunocytochemistry revealed the expression of ASC transporters ASCT1 and ASCT2 in TR-iBRB2 cells. These results suggest that the system ASC at the inner BRB is a potent pathway for supplying serine in the form of the L-isomer from the circulating blood to the retina.

  • systemic route for retinal drug delivery role of the blood retinal Barrier
    2011
    Co-Authors: Masanori Tachikawa, Vadivel Ganapathy, Ken-ichi Hosoya
    Abstract:

    Systemic delivery of therapeutic drugs to the retina is hindered by the presence of the Blood-Retinal Barrier (BRB) which consists of retinal vascular endothelial cells (inner BRB) and retinal pigment epithelial cells (outer BRB). Recent progress in the BRB research has revealed that the BRB expresses a wide variety of transporters essential for the blood-to-retinal influx transport of nutrients and their analogs. At the same time, the BRB also possesses several transporters responsible for the retina-to-blood efflux transport of xenobiotics and drugs, thus being involved in the removal of potentially harmful compounds from the retina. This information can be exploited to our advantage to establish efficient strategies for optimal delivery of clinically relevant therapeutic drugs into the retina.

Yoshiyuki Kubo - One of the best experts on this subject based on the ideXlab platform.

Shin-ichi Akanuma - One of the best experts on this subject based on the ideXlab platform.

  • Recent advances in drug and nutrient transport across the Blood-Retinal Barrier.
    Expert opinion on drug metabolism & toxicology, 2018
    Co-Authors: Yoshiyuki Kubo, Shin-ichi Akanuma, Ken-ichi Hosoya
    Abstract:

    ABSTRACTIntroduction: The Blood-Retinal Barrier (BRB) is the Barrier separating the blood and neural retina, and transport systems for low-weight molecules at the BRB are expected to be useful for ...

  • Localization of organic anion transporting polypeptide (Oatp) 1a4 and Oatp1c1 at the rat Blood-Retinal Barrier.
    Fluids and Barriers of the CNS, 2013
    Co-Authors: Shin-ichi Akanuma, Shiro Hirose, Masanori Tachikawa, Ken-ichi Hosoya
    Abstract:

    Background Organic anion transporting polypeptide (Oatp) transporters at the blood–brain Barrier (BBB) and the Blood-Retinal Barrier (BRB), which consists of retinal capillary endothelial cells and retinal pigment epithelial cells, are major determinants of the control of anionic drugs into the brain and retina. Although Oatp1a4 (Slco1a4) and Oatp1c1 (Slco1c1) are known to be expressed in the abluminal and luminal membrane of the rat BBB and Oatp1a4 is known to be expressed at the BRB, the expression and localization of Oatp1c1 at the BRB and subcellular localization of Oatp1a4 at the BRB have received little attention. Therefore, the purpose of present study was to determine the cellular and subcellular localization of Oatp1a4 and 1c1 at the BRB.

  • Involvement of a Novel Organic Cation Transporter in Verapamil Transport Across the Inner Blood-Retinal Barrier
    Pharmaceutical research, 2012
    Co-Authors: Yoshiyuki Kubo, Shin-ichi Akanuma, Masanori Tachikawa, Yusuke Kusagawa, Ken-ichi Hosoya
    Abstract:

    Purpose To clarify the transport and inhibition characteristics involved in verapamil transport across the inner Blood-Retinal Barrier (inner BRB).

  • Inner Blood-Retinal Barrier mediates l-isomer-predominant transport of serine.
    Journal of Pharmaceutical Sciences, 2011
    Co-Authors: Masanori Tachikawa, Shin-ichi Akanuma, Tetsuya Terasaki, Masashi Okamoto, Shirou Hirose, Daisuke Yoneyama, Ken-ichi Hosoya
    Abstract:

    D-serine, a coagonist for N-methyl-D-aspartate-type glutamate receptors, which mediate visual signal transmission, is thought to be generated from L-serine via serine racemase in the retina. However, the source of L-serine and D-serine in the retina are yet to be determined. The purpose of the present study was to investigate the characteristics of the blood-to-retina transport of serine at the inner Blood-Retinal Barrier (BRB). In vivo study revealed the blood-to-retina transport of [(3) H]L-serine with an influx clearance of 49.9 μL/(min·g retina), which is greater than that of [(3) H]D-serine. This was consistent with the L-isomer-predominant uptake of serine by conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2 cells), an in vitro inner BRB model. [(3) H]L-Serine and [(3) H]D-serine uptake by TR-iBRB2 cells took place in an Na(+)-dependent and a concentration-dependent manner with Michaelis constant values of 97.5 μM and 9.63 mM, respectively. The uptake process of [(3) H]L-serine and [(3) H]D-serine was significantly inhibited by system ASC (alanine-serine-cysteine) substrates. Polymerase chain reaction analysis and immunocytochemistry revealed the expression of ASC transporters ASCT1 and ASCT2 in TR-iBRB2 cells. These results suggest that the system ASC at the inner BRB is a potent pathway for supplying serine in the form of the L-isomer from the circulating blood to the retina.

  • Lipophilicity and Transporter Influence on Blood-Retinal Barrier Permeability: A Comparison with Blood-Brain Barrier Permeability
    Pharmaceutical research, 2010
    Co-Authors: Ken-ichi Hosoya, Shin-ichi Akanuma, Atsushi Yamamoto, Masanori Tachikawa
    Abstract:

    Purpose To determine the lipophilicity trend line from the relationship between the Blood-Retinal Barrier (BRB) permeability and the lipophilicity of permeants and compare it with that of the blood-brain Barrier (BBB).

Henrik Lund-andersen - One of the best experts on this subject based on the ideXlab platform.

  • The Blood-Retinal Barrier permeability to fluorescein in juvenile diabetics treated with continuous subcutaneous insulin infusion.
    Acta Ophthalmologica, 2009
    Co-Authors: Bent Krogsaa, Henrik Lund-andersen, H. H. Parving, T. Lauritzen, Jens Sandahl Christiansen
    Abstract:

    To determine possible quantitative changes of the Blood-Retinal Barrier permeability in juvenile diabetics treated with continuous subcutaneous insulin infusion (CSII), we studied seven patients (three females and four males, mean age 36 years) with a mean duration of the disease of 19 years. The pump treatment was continued for seven to eight days and during the treatment mean blood glucose level decreased to near-normal values (before 13.7 mmol per liter - during 6.2 mmol per liter). There was no changes in retinal appearance during treatment. Determination of the Blood-Retinal Barrier permeability showed no quantitative changes during the one week treatment with CSII (mean permeability before 7.6 10 divided by 7 cm/sec - mean permeability during 7.8 10 divided by 7 cm/sec). In order to quantitate possible long-term reversibility of break-down of the Blood-Retinal Barrier we have design to extend the treatment period.

  • The Blood-Retinal Barrier permeability in essential hypertension.
    Acta ophthalmologica, 2009
    Co-Authors: Bent Krogsaa, Henrik Lund-andersen, H. H. Parving, Peter Bjældager
    Abstract:

    In a series of 8 patients with recently discovered moderate essential hypertension the Blood-Retinal Barrier permeability to fluorescein was determined by aid of quantitative vitreous fluorophotometry before and after normalization of the systemic blood pressure. The permeability before medical treatment was 1.69 X 10(-7) cm/sec (+/- SEM = 0.14) and after medical treatment and normalization of the blood pressure 1.27 X 10(-7) cm/sec (+/- SEM = 0.12), corresponding to the permeability in a normal population. Thus the Blood-Retinal Barrier permeability is pathologically increased even in moderate degrees of essential hypertension, but this increase in permeability is reversible.

  • Breakdown of the Blood-Retinal Barrier in multiple sclerosis measured by vitreous fluorophotometry.
    Acta ophthalmologica, 2009
    Co-Authors: Tine Engell, Bent Krogsaa, Henrik Lund-andersen
    Abstract:

    Periphlebitis retinae in multiple sclerosis appears as transitory cellular infiltrations around veins in an otherwise normal retina. Similar cellular infiltrations have been found around veins in the central nervous system. In the present study the Blood-Retinal Barrier has been investigated by vitreous fluorophotometry. Eight multiple sclerosis patients with actual periphlebitis retinae and 9 patients with previous but not active periphlebitis retinae were included in this study. Abnormal leakage of fluorescein was manifest in the group of multiple sclerosis patients with periphlebitis retinae. Permeability (1.8 +/- 0.2 X 10(-7) cm/sec; mean +/- SEM) but not in the control group as a whole permeability (1.3 +/- 0.1 X 10(-7) cm/sec; mean +/- SEM) compared to 17 normals (permeability 1.1 +/- 0.005). It is thus concluded that breakdown of the Blood-Retinal Barrier may be transitory when connected with periphlebitis retinae in multiple sclerosis.