Jun Arai

Shinshu University, Shonai, Nagano, Japan

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Publications (14)38.41 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the visual outcome 2 years after photodynamic therapy (PDT) in patients with exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Thirty-six eyes undergoing PDT were retrospectively studied. Seventeen eyes of AMD (AMD group) and nineteen eyes of PCV (PCV group) were evaluated. In the AMD group, the mean pre-PDT visual acuity was 0.19. The mean post-PDT visual acuity was 0.16 two years after the PDT. Two years after PDT, the Log MAR visual acuity improved by 0.2 or more in 3 eyes (17.7%), but it decreased by 0.2 or more in 4 eyes (23.5%). In the PCV group, the mean pre-PDT visual acuity was 0.34. The mean post-PDT visual acuity was 0.20 two years after PDT. The Log MAR visual acuity improved by 0.2 or more in 5 eyes (26.3%), but it decreased by 0.2 or more in 7 eyes (36.8%). In this series of patients, more than half of the two groups were able to maintain their visual acuity for 2 years after PDT. Although the average visual acuity of the AMD group was worse than that of the PCV group, the AMD group was able to maintain their visual acuity for 2 years after PDT. The average visual acuity of the PCV group decreased 2 years after PDT.
    Nippon Ganka Gakkai zasshi 01/2009; 112(12):1068-75.
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    ABSTRACT: To determine whether apoptosis of retinal neurons induced by excessive light exposure and ischemia-reperfusion injury is altered in caspase-1 knockout mice. Eight- to 10-week-old caspase-1 knockout mice (Casp1-/-) and wild-type (WT) mice (C57BL/6) were exposed to diffuse, cool, white fluorescent light of 25,000 lux for 2 h. Other mice were subjected to retinal ischemia by increasing the intraocular pressure to 110 mmHg for 45 min. Electroretinograms (ERGs) were recorded before and after the light exposure. TdT-dUTP terminal nick-end labeling (TUNEL) was performed to identify the apoptotic cells after the insults. The inner retinal thickness was measured to evaluate the retinal injury after the ischemia-reperfusion. Expression of caspase-1 protein was studied by immunohistochemical analysis and Western blotting. Caspase-1-like protease activity was determined by a colorimetric tetrapeptide substrate. The morphology of the retina and the amplitudes of the a and b waves of the ERGs of Casp1-/- mice did not differ from those of WT mice. After the light exposure, TUNEL-positive cells were observed in the outer nuclear layer of the WT mice retina. The number of TUNEL-positive photoreceptor nuclei after the light exposure, and the number of nuclei in the inner nuclear layer after the ischemia-reperfusion injury, were significantly less in Casp1-/- mice than in WT mice. There were more caspase-1-positive photoreceptor cells in WT mice after the light injury. The inner retinal layer of Casp1-/- mice was significantly thicker in Casp1-/- mice than in WT mice 2 weeks after the ischemic insult. Retinal neuronal apoptosis was less prominent in Casp1-/- mice after excessive light exposure and ischemia-reperfusion injury. These data indicate that caspase-1 plays a role in retinal neuronal apoptosis.
    Japanese Journal of Ophthalmology 01/2006; 50(5):417-25. · 1.27 Impact Factor
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    ABSTRACT: To study the genotypes, allelic frequencies, and polymorphisms of apolipoprotein E (Apo E) in unrelated Japanese patients with polypoidal choroidal vasculopathy (PCV) or exudative age-related macular degeneration (AMD) and control subjects without macular degeneration. Cross-sectional study. Blood samples from 225 subjects older than 50 years were used. The 225 subjects included 58 patients with PCV, 85 with AMD, and 82 without macular degeneration. Coding exons of the Apo E gene were amplified by polymerase chain reaction, and the DNA sequences were determined by direct sequencing with an automated sequencer. Apo E epsilon3/epsilon3 was the most frequent genotype with a prevalence of 79.3% in PCV patients, 76.5% in AMD patients, and 67.1% in the control subjects. However, the differences in the percentages were not statistically significant among the three groups. The most frequently found allele in the three groups was epsilon3. Patients with PCV and AMD were less likely to have epsilon2 and epsilon4 than the control subjects, but the differences were not statistically significant. Five minor Apo E single nucleotide polymorphisms, including epsilon5 and epsilon7, were found. Japanese patients with PCV and AMD were less likely to have epsilon2 and epsilon4 polymorphisms, but the differences from the normals were not statistically significant for the Apo E genotypes and allelic frequencies.
    American Journal of Ophthalmology 11/2004; 138(4):567-73. · 4.02 Impact Factor
  • Retina 07/2003; 23(3):417-20. · 2.83 Impact Factor
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    British Journal of Ophthalmology 07/2003; 87(6):795. · 2.73 Impact Factor
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    ABSTRACT: PTB-like protein (PTBLP) is a new homologue of pyrimidine tract binding protein (PTB), and has been cloned as a possible autoantigen in cancer-associated retinopathy. PTBLP has two functional domains, the nuclear localization signal and the RNA recognition motifs (RRMs). Full-length PTBLP (PTBLP-L) has four RRMs, and its alternative splicing product (PTBLP-S) lacks the third and fourth RRMs. Although PTBLPs are expressed in neuronal tissues, the function of PTBLPs has not been determined. We have studed whether PTBLP plays a role in neuronal differentiation using PC12 cells. During the process of nerve growth factor-induced neuronal differentiation of PC12 cells, PTBLP-L was down-regulated whereas PTBLP-S was up-regulated. Transfection of PTBLP-L into PC12 cells led to the suppression of neuronal differentiation. In PTBLP-S transfected cells, however, this suppression was not evident. When both PTBLP-L and PTBLP-S were co-transfected, the suppressive effect of PTBLP-L decreased. In differentiated cells, PTBLP-S localized in the nucleus and PTBLP-L was found dispersed throughout the cytoplasm and neuronal growth cone. These findings suggest that PTBLP-L acts as a negative regulator of neuronal differentiation and PTBLP-S acts as a competitor of PTBLP-L.
    Journal of Biochemistry 07/2002; 131(6):861-8. · 3.07 Impact Factor
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    ABSTRACT: To report characteristics of polypoidal choroidal vasculopathy (PCV) of large vascular networks that expand across the retinal vascular arcade. Among 60 consecutive eyes diagnosed as having PCV by fluorescein and indocyanine green (ICG) angiography, 12 eyes (9 patients) showed large lesions. The clinical and angiographic features of these 12 eyes were studied retrospectively. Cases of large PCV typically showed dilated network vessels, which spread radially, and multiple polypoidal dilations at the end of the network vessels. Most of the polypoidal dilations formed clusters resembling bunches of grapes and caused large serous and/or hemorrhagic pigment epithelial detachments (PEDs). Among the 12 eyes, 5 showed rapid expansion of the lesions and became large PCVs within 3-24 months. In these eyes, ICG angiography revealed mesh-like choroidal vessels beneath the retinal pigment epithelium. PCV with a large vascular network that expands across the vascular arcade is not uncommon. Some of these cases seems to have characteristics of choroidal neovascularization rather than choroidal vasculopathy. It is not easy to distinguish such cases from exudative age-related macular degeneration even though they showed typical findings of PCV on ICG angiography.
    Albrecht von Graæes Archiv für Ophthalmologie 06/2002; 240(5):354-61. · 1.93 Impact Factor
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    ABSTRACT: To evaluate a new delivery system of 5-fluorouracil (5-FU) using 5-fluorocytosine (5-FC) as a prodrug and cytosine deaminase induced in vitro and in vivo. Fibroblastic cells from rabbit Tenon's capsule were cultured. The cells were exposed to 5-FU and 5-FC with or without cytosine deaminase induced by recombinant adenovirus. In the in vitro study, cell proliferation and DNA synthesis were assessed by MTS, BrdU assay. The effect of 5-FC removal after the treatment of 5-FC and cytosine deaminase induction was also assayed. In the in vivo study cells with or without cytosine deaminase induction were transplanted into the subconjunctival space of mice, followed by eye drops of 1000 microg/ml of 5-FC three times a day. The mice were sacrificed at days 1, 5, and 10, then the cells transplanted were evaluated. Cell proliferation was inhibited by exposure to 5-FU in a dose dependent manner; however, up to 1000 microg/ml of 5-FC did not affect cell proliferation. Cell proliferation was inhibited by exposure to 5-FC in a time dependent manner with induction of cytosine deaminase following infection of recombinant adenovirus. When 5-FC was removed 3 or 6 days after the treatment, the cells grew again. The effect was reproduced in the in vivo model of subconjunctival cellular proliferation although 5-FC was administrated as eye drops. There were no cases with corneal erosion. Cell proliferation was inhibited by co-exposure of 5-FC and cytosine deaminase. This new delivery system may merit controlled delivery of 5-FU after filtering surgery.
    British Journal of Ophthalmology 06/2002; 86(5):581-6. · 2.73 Impact Factor
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    ABSTRACT: To investigate the expression and possible neuroprotective effects of hepatocyte growth factor (HGF) in a rat model of retinal ischemia-reperfusion injury. Retinal ischemia was induced in adult male Sprague-Dawley rats by raising the intraocular pressure to 110 mm Hg for 45 minutes. To study expression of HGF and its receptor c-Met, reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis, and immunohistochemical staining were performed on eyes enucleated at 6, 12, 24, 48, and 96 hours after reperfusion. To examine the neuroprotective effects of HGF, recombinant human (rh)HGF (1, 6, and 12 microg in 2 microL PBS) or vehicle was administered intravitreally 1 minute after reperfusion, and the eyes were enucleated at 6, 12, 24, 48, and 96 hours and 28 days after reperfusion. The retinal damage was assessed by electroretinogram (ERG) recordings, by measuring the inner retinal thickness, and by counting the number of TUNEL-positive cells in each retinal layer. RT-PCR and Western blot analyses showed upregulation of HGF and c-Met-HGF receptor mRNA at 6, 12, 24, and 48 hours after reperfusion, compared with the normal rat retina. Immunohistochemically, expression of HGF was found in the retinal pigment epithelial cells at 6 hours after reperfusion and in some cells in the ganglion cell layer and inner nuclear layer at 24 hours after reperfusion. The amplitudes of the ERG b-wave and oscillatory potentials were significantly larger in the eyes treated with 6 and 12 microg rhHGF than in those of vehicle-treated control rats (P < 0.01). On day 28, the thicknesses of the inner retina of vehicle-treated rats and that of 6-microg rhHGF-treated rats were 54.4 +/- 6.12 (mean +/- SD, n = 9) and 71.5 +/- 9.81 microm (n = 8), respectively (P < 0.01). The number of TUNEL-positive cells at 6, 12, 24, and 48 hours after reperfusion was decreased significantly by treatment with 6 microg rhHGF, compared with those in the control rats (P < 0.01). Upregulation of HGF in the retina may play a role in retinal ischemia-reperfusion injury. Intravitreal injection of rhHGF is neuroprotective against the injury.
    Investigative Ophthalmology &amp Visual Science 02/2002; 43(2):528-36. · 3.44 Impact Factor
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    ABSTRACT: To report that optical coherence tomography as early as 24 hours after macular hole surgery shows anatomic configuration of the closed macular holes. In a prospective study, seven eyes of seven consecutive patients with stage 3 or 4 idiopathic macular hole underwent surgery. Optical coherence tomography was performed preoperatively and at 24, 48, and 72 hours after the surgery. Optical coherence tomography images could be obtained on four out of the seven eyes at 24 hours after surgery. These images showed anatomic configuration of the closed macular holes. Surgical success was confirmed in all of the eyes when the gas was completely absorbed. Optical coherence tomography revealed anatomic configuration of surgically closed macular holes within 24 hours after successful surgery.
    American Journal of Ophthalmology 12/2000; 130(5):675-6. · 4.02 Impact Factor
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    ABSTRACT: Cancer-associated retinopathy (CAR) is a rare form of retinal degeneration and also one of the paraneoplastic neurologic disorders. Sera of CAR patients usually contain high titers of antibodies against retinal proteins, and CAR is believed to be an autoimmune disease. Using serum from a CAR patient as a molecular probe, a homologue of the polypyrimidine tract-binding protein (PTB) was isolated from a cDNA library of rat neonatal retina. This homologue, named PTB-like protein (PTBLP), encodes a 532 amino acid residue protein and has 73.5 and 68.8% homology with PTB and with a regulator of differentiation 1, respectively. Functional domains in the PTB, such as nuclear localization signals and four RNA recognition motifs (RRMs), were highly conserved. The expression of PTBLP mRNA was observed in the retina and brain but not in liver, kidney, spleen, or lung. The expression of PTBLP protein in rat retina was distributed in most of the cells in the ganglion cell layer and some cells in the inner nuclear layer. The PTBLP protein was localized in the nuclei of these cells. These results suggest that PTBLP is a new member of the PTB gene family and a neuron-specific homologue.
    Journal of Biochemistry 12/2000; 128(5):811-21. · 3.07 Impact Factor
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    ABSTRACT: Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome that is characterized by retinal degeneration. Two cDNA clones, recoverin and tubby-like protein 1 (TULP1), were isolated from a human retinal cDNA library by using serum from a CAR patient as the probe. Both recoverin and TULP1 are retina-specific protein, and TULP1 is a member of tubby gene family. A determination of the recognized amino acid sequence of TULP1 by the patient serum and immunohistochemical studies on the distribution of TULP1 in the retina were done in this study.
    Journal of Neuroimmunology 03/2000; 103(1):26-33. · 3.03 Impact Factor
  • Retina 02/2000; 20(6):674-6. · 2.83 Impact Factor
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    ABSTRACT: To study the role of caspase-like proteases, especially roles of more extensively characterized caspase-1 and caspase-2, in apoptotic photoreceptor cell degeneration in Royal College of Surgeons (RCS) rats. Both RCS and Sprague-Dawley rats were used. Cryosections of the retinas at various postnatal times were immunostained with antibodies against caspase-1 (interleukin-1beta-converting enzyme, ICE) and caspase-2 (Nedd2/Ich-1). Double staining with TdT-dUTP terminal nick-end labeling (TUNEL), propidium iodide, and the antibodies was also performed. To evaluate the time course of protein expression, western blot analysis was carried out. The temporal profile of caspase-like protease activity was studied using a fluorogenic tetrapeptide substrate, acetyl-tyrosyl-valyl-alanyl-aspartic acid alpha (4-methyl-coumaryl-7-amide) (Ac-YVAD-MCA). Intravitreal injection of a caspase-1 inhibitor, acetyl-tyrosyl-valyl-alanyl-aspartic-aldehyde (Ac-YVAD-CHO), at postnatal days 21 (P21) and P26 was performed to see if this caused a decrease in apoptotic cell number at P28. TUNEL-positive photoreceptors of RCS rats stained strongly with antibodies against caspase-1 and caspase-2. Double staining studies revealed that caspase-1 and caspase-2 were coexpressed in apoptotic cells. Western blot analysis showed that active forms of caspase-1-like and caspase-2-like proteases were upregulated at P28, concurrent with the peak in TUNEL-positive cells. The enzymatic activity of caspase-1-like protease was elevated in RCS rat retinas at P28, and the inhibitor of caspase-1 transiently reduced the number of the apoptotic photoreceptors. Activation of caspase-like proteases plays an important role in photoreceptor apoptosis of RCS rats.
    Investigative Ophthalmology &amp Visual Science 08/1999; 40(8):1802-7. · 3.44 Impact Factor