Nagahisa Yoshimura

Optical coherence tomograghy to confirm early closure of macular holes

PURPOSEnTo report that optical coherence tomography as early as 24 hours after macular hole surgery shows anatomic configuration of the closed macular holes.nnnMETHODnIn 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.nnnRESULTSnOptical 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.nnnCONCLUSIONnOptical coherence tomography revealed anatomic configuration of surgically closed macular holes within 24 hours after successful surgery.

Tranilast inhibits the proliferation, chemotaxis and tube formation of human microvascular endothelial cells in vitro and angiogenesis in vivo

1 First developed as an antiallergic drug, tranilast inhibits chemical mediator release from mast cells. In the present study, we examine the effects of tranilast on angiogenesis in vitro and in vivo and discuss the application of tranilast for angiogenic diseases. 2 Tranilast inhibited significantly the proliferation (IC50: 136u2003μM, 95% confidence limits: 124–137u2003μM) and vascular endothelium growth factor (VEGF)‐induced chemotaxis (IC50: 135u2003μM, 95% confidence limits: 124–147u2003μM) of human dermal microvascular endothelial cells (HDMECs) at concentrations greater than 25u2003μgu2003ml−1. No toxicity to HDMECs measuring by LDH release and no inhibitory effects on metalloproteinase (MMP)‐2 and MMP‐9 activity were observed even at 100u2003μgu2003ml−1 (306u2003μM). 3 Tube formation of HDMECs cultured on the matrigel as an in vitro angiogenesis model was inhibited by tranilast in a concentration‐dependent manner. The IC50 value and 95% confidence limits were 175u2003μM and 151–204u2003μM, respectively. 4 In vivo angiogenesis was induced in mice by the subcutaneous injection of matrigel containing 30u2003ngu2003ml−1 VEGF and 64u2003μgu2003ml−1 heparin. Tranilast was administered orally twice a day for 3 days. Tranilast dose‐dependently suppressed angiogenesis in the matrigel and a significant change was observed at a dose of 300u2003mgu2003kg−1. 5 These results indicate that tranilast is an angiogenesis inhibitor which may be beneficial for the improvement of angiogenic diseases such as proliferative diabetic retinopathy, age‐related macular degeneration, tumour invasion and rheumatoid arthritis.

Transplantation of adult rat hippocampus-derived neural stem cells into retina injured by transient ischemia

Neural stem cells are capable of differentiating along multiple central nervous system cell-type lineages, and their use as graft material has provided new strategies for the treatment of neuronal damage. We transplanted adult rat hippocampus-derived neural stem cells into eyes of adult rats that underwent ischemia-reperfusion injury. As control, the cells were also injected into normal rats eyes without ischemic insult. The rats were sacrificed at 1, 2, 4, and 8 weeks, and the eyes were examined histochemically. In eyes with the insult, the transplanted cells were well integrated into the host retinas and expressed Map2ab. In the control, none of the cells migrated into the retina. These results suggest that neural stem cells may be used as donor cells for transplantation to repair ischemic-injured retina.

Pathological features of surgically excised polypoidal choroidal vasculopathy membranes

The histopathological features are reported of surgically excised specimens from five patients with polypoidal choroidal vasculopathy, which had been diagnosed by indocyanine green angiography. On stereomicroscopy, four of the five cases demonstrated large choroidal arterioles with an inner elastic layer. Disruption of the inner elastic layer and arteriosclerotic changes of the vessels were identified by light microscopy. Transmission electron microscopy demonstrated increased deposition of basement membrane‐like material, together with collagen fibres, in the arteriolar walls. This study indicates that large choroidal arterioles and venules can be found in excised specimens from patients with polypoidal choroidal vasculopathy and arteriosclerosis is an important pathological feature.

Ocular manifestations in Blau syndrome associated with a CARD15/Nod2 mutation

PURPOSEnTo report cases of Blau syndrome with a CARD15/Nod2 mutation.nnnDESIGNnObservational and interventional case report.nnnPARTICIPANTSnA 10-year-old Japanese boy (proband) was seen with secondary angle-closure glaucoma (iris bombe), uveitis, skin rashes, and camptodactyly. His sister had posterior synechia and camptodactyly. She had iritis in both eyes during the follow-up period. Both eyes of the father were phthisical because of granulomatous uveitis and secondary glaucoma. The father also had camptodactyly.nnnMETHODSnSurgery was performed to release the iris bombe. Ocular inflammation was treated by topical and systemic steroids. Biopsy specimens from the skin rash and from the iris (from iridectomy) were obtained from the proband. Genetic analyses were performed on the proband, his sister, and their mother for a CARD15/Nod2 mutation.nnnMAIN OUTCOME MEASURESnClinical features, pathologic findings of the skin and iris specimens, and genetic analysis of the CARD15/Nod2 gene.nnnRESULTSnPhacoemulsification, intraocular lens implantation, and peripheral iridectomy released the iris bombe. The biopsy specimen from the skin rash showed noncaseating, granulomatous infiltration with epithelioid cells and lymphocytes. The iridectomy specimen showed nonspecific inflammation. Systemic and topical steroid therapy partly reduced the ocular inflammation. Genetic analyses showed that the proband and his sister had an R334W mutation in the CARD15/Nod2 gene, but their mother was of the wild type.nnnCONCLUSIONSnBlau syndrome should be considered in the differential diagnosis of childhood uveitis. Genetic analysis of the CARD15/Nod2 gene is helpful in the diagnosis.

Tubby-like protein 1 as an autoantigen in cancer-associated retinopathy.

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.

Increased Cytokine Gene Expression in Rat Retina following Transient Ischemia

Tumor necrosis factor (TNF) gene expression in rat retina following transient ischemia was studied by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Gene expression for other cytokines was also studied by RT-PCR. Although very little expression for TNF gene was detected in normal retina, it was markedly increased 0.5-48 h after reperfusion, with peak expression at 12 h (20-fold of control). Gene expression for interleukin-6, interferon-gamma, and transforming growth factor-beta 1 was also increased. The results provide evidence that retinal ischemia can up-regulate cytokine gene expression in the retina.

Platelet-derived growth factor gene expression in cultured human retinal pigment epithelial cells

Gene expression of platelet-derived growth factor (PDGF) and its receptors in cultured human retinal pigment epithelial (RPE) cells was studied by using semiquantitative polymerase chain reaction. The RPE cells were found to express PDGF A- and B-chain genes as well as alpha- and beta-receptor genes with dominant expression of B-chain and beta-receptor isoforms. Phorbol myristate acetate (PMA) and thrombin increased the expression of PDGF B-chain gene to 19.8 +/- 1.75 and 15.9 +/- 1.84 fold (n = 3) of the control without affecting beta-receptor gene expression. PDGF produced by the RPE cells may play an important role in the pathogenesis of some ocular proliferative diseases.

Polypoidal choroidal vasculopathy with large vascular network

AbstractPurpose. To report characteristics of polypoidal choroidal vasculopathy (PCV) of large vascular networks that expand across the retinal vascular arcade.n Methods. 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.n Results. 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.n Conclusion. 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.

Diagnosis of intraocular lymphoma by polymerase chain reaction

Abstract• Background: Cytopathological examinations have been used in the diagnosis of intraocular lymphoma. However, sometimes it is not easy to detect malignant cells in the biopsy specimens. We applied a method that identified monoclonal proliferation of B lymphocytes by using polymerase chain reaction (PCR) in the diagnosis of patients suspected to have intraocular B-cell lymphoma. • Methods: Threè specimens of the diagnostic vitrectomy were studied by cytological examination and by PCR to amplify the complementary determining region (CDR3) of immunoglobulin heavy chain (IgH) gene. As a positive control, a biopsy specimen of an orbital lymphoma was examined; four vitrectomy specimens from patients with diabetic retinopathy, proliferative vitreo-retinopathy, acute retinal necrosis (ARN) and macular hole were negative controls. • Results: On cytologic examination, no malignant cells were found in three specimens: suspected intraocular lymphoma and one ARN. In contrast, a discrete band that reflected monoclonal proliferation of B lymphocytes was detected by PCR in specimens from two patients and the positive control. Vitrectomy specimens from the negative controls, including ARN, did not show a discrete band on PCR. • Conclusions: Two cases of ocular malignant lymphoma were diagnosed by PCR identification of monoclonal proliferation of B lymphocytes. This method may be an additional diagnostic tool in the diagnosis of intraocular B-cell lymphoma.