-
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE: Multidrug resistance protein 4 (MRP4) effluxes a wide variety of endogenous compounds, including cyclic adenosine monophosphate (cAMP), and is exclusively expressed in vascular endothelial cells (ECs) of the retina. This study aimed to investigate the role of MRP4 in retinal vascular development. Methods: The retinal vascular phenotype of Mrp4-/- mice was examined by whole-mount immunohistochemistry at P3, P6, and P14. The retinas from P6 pups that received an intraperitoneal injection of either solvent control or forskolin, an inducer of intracellular cAMP formation, at P4 and P5 were analyzed in terms of their vascular formation (vascular length, vascular branching, vascular density and the number of tip cells), cell proliferation and apoptosis, and vessel stability. Results: The Mrp4-/- mice exhibited no overt abnormalities in the development of the retinal vasculature, but retinal vascular development in the Mrp4-/- mice was suppressed in response to forskolin administration. There was a significant decrease in the vascular length, vascular branching, and vascular density and inhibited tip cell formation at the vascular front. The forskolin-treated Mrp4-/- mice showed an increased number of Ki67-positive and cleaved caspase 3-positive ECs, a significant decrease in the amount of pericyte coverage, and a reduced number of empty sleeves. In pups exposed to hyperoxia (75% oxygen) from P7 to P12, the Mrp4-/- mice showed a significant increase in the unvascularized retinal area. Conclusions: Mrp4-/- mice exhibited suppressed retinal vascular development in response to forskolin treatment. Thus, Mrp4 might have protective roles in retinal vascular development by regulating the intracellular cAMP level.
Investigative ophthalmology & visual science 11/2012; · 3.43 Impact Factor
-
Japanese Journal of Ophthalmology 06/2011; 55(5):585-7. · 0.92 Impact Factor
-
Kazumichi Fujioka,
Ichiro Morioka,
Kandai Nozu,
Masashi Nishimoto,
Mariko Amano, Mizuki Tagami,
Shigeru Honda,
Naoki Yokoyama,
Hideto Yamada,
Kazumoto Iijima,
Masafumi Matsuo
Pediatrics International 06/2011; 53(3):406-8. · 0.63 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the retinal toxicity of intravitreal tissue plasminogen activator (tPA) injection for branch and central retinal vein occlusion (BRVO and CRVO) using the electroretinogram (ERG).
Ten BRVO patients and 5 CRVO patients were enrolled. A complete examination including full-field ERG, visual acuity, central retinal thickness (CRT), and evaluation of systemic and ocular complications was performed before and after intravitreal tPA injection.
No significant differences were found in the amplitude or implicit time of any ERG component after tPA injection, and no systemic or ocular complication was observed. The improvement of visual acuity was significant at month 3 in the BRVO group (p < 0.05) but not in the CRVO group. CRT significantly decreased over the course of 3 months in both groups (p < 0.01).
Intravitreal tPA injection seems to be a safe and effective treatment option for macular oedema caused by retinal vein occlusions.
Ophthalmologica 05/2011; 226(2):81-6. · 1.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The multidrug resistance protein (MRP) MRP4/ABCC4 is an ATP-binding cassette transporter that actively effluxes endogenous and xenobiotic substrates out of cells. In the rodent retina, Mrp4 mRNA and protein are exclusively expressed in vascular endothelial cells, but the angiogenic properties of Mrp4 are poorly understood so far. This study aims to explore the angiogenic properties of MRP4 in human retinal microvascular endothelial cells (HRECs) utilizing the RNA interference (RNAi) technique. MRP4 expression was decreased at the mRNA and protein levels after stimulation with exogenous vascular endothelial growth factor in a dose-dependent manner. RNAi-mediated MRP4 knockdown in HRECs do not affect cell proliferation but enhances cell migration. Moreover, cell apoptosis induced by serum starvation was less prominent in MRP4 siRNA-treated HRECs as compared to control siRNA-treated HRECs. In a Matrigel-based tube-formation assay, although MRP4 knockdown did not lead to a significant change in the total tube length, MRP4 siRNA-treated HRECs assembled and aggregated into a massive tube-like structure, which was not observed in control siRNA-treated HRECs. These results suggest that MRP4 is uniquely involved in retinal angiogenesis.
Biochemical and Biophysical Research Communications 10/2010; 400(4):593-8. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE: To describe the ophthalmic findings in the fundus of a Japanese infant with Potter sequence having a mutation in the PAX2 gene. METHODS: A 1-month-old infant diagnosed with Potter sequence who had bilateral renal hypoplasia and a mutation in the PAX2 gene was subjected to detailed ophthalmic examination. RESULTS: Funduscopy revealed a megalopapilla with marked excavation in the right eye. The left optic disc showed a similar abnormality, but to a lesser extent. B-mode ultrasonography and magnetic resonance imaging detected giant cystic lesions occupying the optic nerve head in both eyes. According to these results, we diagnosed this patient as having papillorenal syndrome (PRS) associated with a PAX2 mutation. CONCLUSIONS: This report shows ophthalmic findings in the youngest patient with PRS and PAX2-associated Potter sequence. Optic disc anomalies may be involved in some infants with Potter sequence. We anticipate an increase in opportunities for ophthalmic examinations in infants with diseases such as Potter sequence with previously high mortality rates.
Case reports in ophthalmology. 01/2010; 1(2):94-98.
-
[show abstract]
[hide abstract]
ABSTRACT: ATP-binding cassette (ABC) transporters at the blood-brain barrier (BBB) are responsible for the majority of the transcellular movement of various substrates, including various drugs, and contribute to the maintenance of brain homeostasis. Clinically, the abnormal expression of efflux transporters at the BBB is known to be associated with brain diseases such as epilepsy. In the retina, vascular endothelial cells outline the inner blood-retinal barrier (BRB) like the BBB, and some ABC efflux transporters are expressed in the adult retina. However, little is known about ABC transporter expression during retinal development or under pathological conditions. Here, we examined ABC transporter expression in the mouse retina, and demonstrated that P-glycoprotein (P-gp)/ABCB1, Mrp4/ABCC4, and Bcrp/ABCG2 were almost uniformly expressed in these blood vessels, including the capillaries and large vessels. This expression persisted throughout the developmental period, and the hyaloid vessels that normally feed the developing eye were immunoreactive for P-gp and Mrp4. Furthermore, we investigated ABC transporter expression in pathological angiogenesis using an oxygen-induced retinopathy model where hypoxia-induced preretinal neovascularization occurred around the central avascular retina. P-gp was prominently immunoexpressed but Mrp4 and Bcrp were weakly immunoexpressed, in the preretinal neovascular tufts. These findings will be helpful for understanding the roles of ABC transporters during both physiological and pathological retinal angiogenesis, and might provide new insights for safe and effective drug administration to infants or patients with angiogenic ocular disease.
Brain research 07/2009; 1283:186-93. · 2.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To report a case of familial exudative vitreoretinopathy (FEVR) rapidly resolved by intravitreal injection of bevacizumab.
A 36-year-old woman complained about floaters and visual field defect. Funduscopic examinations revealed retinal vessel anastomosis located between the equator and ora serrata in both eyes. The right eye was accompanied with slight vitreous hemorrhage. Since the patient declined retinal cryopexy for cosmetic reasons, intravitreal bevacizumab injections (1.25 mg/0.05 ml) were performed in both eyes.
Treatment resulted in the rapid regression and the accelerated fibrosis of neovascular tissues. At 4-month follow-up in the right eye and 1-month follow-up in the left, no signs of systemic or ocular complications were detected.
Intravitreal injection of bevacizumab may be considered as an alternative method in treating FEVR.
Albrecht von Graæes Archiv für Ophthalmologie 10/2008; 246(12):1787-9. · 2.17 Impact Factor
