Increased Microcirculation on Optic Nerve Head by Laser Speckle Flowgraphy at Early Stage of Leber Hereditary Optic Neuropathy.

Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder predominantly affecting young men. Characteristic features of an early stage of LHON are peripapillary telangiectatic microangiopathy with optic disc hyperaemia and swelling of the retinal nerve fibre layers. We evaluated the microcirculation of the optic nerve head (ONH) by laser speckle flowgraphy (LSFG) in a 79-year-old man and a 36-year-old woman with LHON.

Visual prognosis better in eyes with less severe reduction of visual acuity one year after onset of Leber hereditary optic neuropathy caused by the 11,778 mutation.

Background: Patients with Leber hereditary optic neuropathy (LHON) have a progressive decrease of their visual acuity which can deteriorate to <0.1. Some patients can have a partial recovery of their vision in one or both eyes.

Efficient intradermal delivery of superoxide dismutase using a combination of liposomes and iontophoresis for protection against UV-induced skin damage.

Superoxide dismutase (SOD) is a potent antioxidant agent that protects against UV-induced skin damage. However, its high molecular weight is a significant obstacle for efficient delivery into the skin through the stratum corneum and development of antioxidant activity. Recently, we developed a non-invasive transfollicular delivery system for macromolecules using a combination of liposomes and iontophoresis, that represents promising technology for enhancing transdermal administration of charged drugs (IJP, 403, 2011, Kajimoto et al.

Noninvasive and efficient transdermal delivery of CpG-oligodeoxynucleotide for cancer immunotherapy.

Oligodeoxynucleotides containing unmethylated cytosine-phosphate-guanosine motifs (CpG-ODN) possess immunostimulatory effects and potential antitumor activity. Since the skin is an easily available site of administration of CpG-ODN due to its accessibility and the presence of abundant antigen presenting cells, it is expected that the application of CpG-ODN to the skin would induce systemic immune response and antitumor activity. However, it is difficult to deliver hydrophilic macromolecules including CpG-ODN through the skin.

Noninvasive and persistent transfollicular drug delivery system using a combination of liposomes and iontophoresis.

Iontophoresis is a promising technique for enhancing transdermal administration of charged drugs. However, conventional iontophoresis is not sufficient for effective delivery of large, hydrophilic, or electrically neutral molecules. In this study, we utilized charged liposomes as carriers, focused on a transfollicular route for delivery of the liposomes, and optimized iontophoretic conditions and lipid composition for this method in both in vitro and in vivo conditions.

Noninvasive delivery of siRNA into the epidermis by iontophoresis using an atopic dermatitis-like model rat.

Topical application of siRNA to the skin should be an effective treatment for serious skin disorders, such as atopic dermatitis. However, it is difficult to introduce hydrophilic macromolecules, including siRNA, into the skin by conventional methods. For efficient delivery of siRNA, we examined an iontophoretic technique, since it is suitable for the delivery of charged molecules.

In vivo transdermal delivery of diclofenac by ion-exchange iontophoresis with geraniol.

A novel iontophoretic system utilizing ion-exchange membranes is effective for selective transdermal delivery of ionized drugs. In the present study, we examined in vivo availability and safety of ion-exchange iontophoresis in the transdermal delivery of anionic diclofenac, a well known anti-inflammatory medication, to rat dorsal skin. While iontophoresis increased the plasma concentration of diclofenac sodium and skin injury was not observed, no anti-inflammatory effect was exerted.

[A case report illustrating the effectiveness of reading performance assessments in the diagnosis and treatment of psychogenic visual disturbances].

Purpose: An optimal strategy for treating psychogenic visual disturbances in adults has not been established. We report a patient with psychogenic visual disturbances who recovered his visual acuity and showed an improvement in his reading performance after undergoing training based on a reading performance assessment.

Case: A 37-year-old man who had been diagnosed as having myopic macular degeneration was referred to our clinic.

Purification, molecular cloning, and expression of a novel growth-promoting factor for retinal pigment epithelial cells, REF-1/TFPI-2.

Purpose: Retinal pigment epithelial (RPE) cells are known to play important roles in maintaining the homeostasis of the retina and in controlling choroidal neovascularization. The purpose of this study was to identify a factor or factors that would stimulate RPE cells to proliferate.

Methods: To isolate such a factor, 100 L of human-fibroblast-conditioned medium underwent ion-exchange, hydrophobic, and reverse-phase chromatographies followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

[Two cases of digitalis toxicity with reversible and severe decrease of visual acuity].

Background: We performed electrophysiologic tests on two patients with digitalis toxicity who first had photophobia and xanthopsia and revealed reversible reduced visual acuity and binocular central scotoma.

Cases: The patients were a 72-year-old male and a 54-year-old male who had symptoms of digitalis toxicity.

Findings: The corrected visual acuity was severely decreased during digitalis toxicity, 0.

Do idebenone and vitamin therapy shorten the time to achieve visual recovery in Leber hereditary optic neuropathy?

Objectives: The authors investigated the effectiveness of idebenone combined with vitamin B2 and vitamin C in the treatment of patients with Leber hereditary optic neuropathy (LHON) in an early stage as compared with untreated patients with LHON. These agents may stimulate the formation of ATP.

Materials And Methods: For this retrospective study, the authors selected 28 outpatients with LHON from the Keio University Hospital.

Collagen production by cultured human retinal pigment epithelial cells.

We investigated extracellular matrix produced by human retinal pigment epithelial cells (RPE) in vitro using electron microscopy and enzyme linked immunosorbent assay (ELISA). The thickness of the matrix under the cell layer was about 30 microns after 360 days of culture. It consisted mainly of fibrous and granular components.

Retinal pigment epithelial cell-based gene therapy against hemoglobin toxicity.

To determine if overexpression of the human heme oxygenase (HO-1) protects retinal pigment (RPE) cells from hemoglobin toxicity, a human RPE cell line was infected by an adenoviral vector containing the HO-1 (Ad-HO-1) gene or transfected with a plasmid containing the cytomegalovirus promoter and HO-1 cDNA (pRc/CMV-HO-1) complexed to cationic liposomes. Phase contrast microscopy and acid phosphatase activity were examined to insure homogeneity of the cell line. Mitochondrial cytochrome and microsomal heme content were measured in both transduced and control cells.

Spectrum of pathogenic mitochondrial DNA mutations and clinical features in Japanese families with Leber's hereditary optic neuropathy.

Purpose: To investigate the incidence and clinical significance of primary or proposed secondary mitochondrial DNA (mtDNA) mutations in Japanese patients with Leber's hereditary optic neuropathy (LHON).

Methods: Blood samples from the 80 unrelated Japanese patients with bilateral optic atrophy were screened for primary LHON mutations. Patients found to have a primary LHON mutation were then tested for 9 proposed secondary LHON mutations.

Two genes, COL4A3 and COL4A4 coding for the human alpha3(IV) and alpha4(IV) collagen chains are arranged head-to-head on chromosome 2q36.

We first isolated and characterized genomic DNA fragments that cover the 5' flanking sequences of COL4A3 and COL4A4 encoding the human basement membrane alpha3(IV) and alpha4(IV) collagen chains, respectively. Nucleotide sequence analysis indicated that the two genes are arranged head-to-head. To determine transcription start site for COL4A4 gene, we performed RACE and RNase protection assays, indicating that there are two alternative transcripts presumably derived from two different promoters.

High incidence of visual recovery among four Japanese patients with Leber's hereditary optic neuropathy with the 14484 mutation.

The 14484 mutation in the ND6 gene of mitochondrial DNA (mtDNA) is a genetic mutation associated with Leber's hereditary optic neuropathy (LHON) in Caucasian patients who show a high incidence of visual recovery. We evaluated four Japanese patients with LHON associated with the 14484 mutation who were negative for eight proposed secondary mutations. There was no family history of optic atrophy in three of the four patients.

[Detection of mycobacterial DNA with polymerase chain reaction in eye discharge and gastric juices in a case of scleritis].

We report a case of mycobacterial scleritis in which prompt diagnosis was made by the detection of mycobacterial DNA with polymerase chain reaction (PCR) in eye discharge and gastric juices, when conventional tests were negative. A 77-year-old woman who had a past history of pulmonary tuberculosis visited the outpatient clinic of Tokai University Hospital complaining of pain in her right eye. She was diagnosed as having scleritis and uveitis.

[A histopathological study of corneal amyloidosis secondary to trichiasis].

We present a case of secondary corneal amyloidosis whose etiological mechanism was investigated by immunohistochemistry and electron microscopy. A 48-year-old woman had suffered from trichiasis in the right eye for 35 years, and developed secondary corneal amyloidosis, a phenomenon previously described but whose etiological mechanism has not been explained. Slitlamp examination of the cornea revealed a white excrescence with a diameter of 2 mm.

[Evaluation of risk factors of interferon-associated retinopathy in patients with type C chronic active hepatitis].

The risk factors of retinopathy associated with administration of interferon have not been fully clarified. We prospectively examined the retinal condition in 50 patients with type C chronic active hepatitis during alpha-interferon treatment. 43 patients (86%) were shown to have retinopathy during the course of interferon treatment, and were divided into three groups.

Inhibition of corneal ulceration by tetrapeptidyl hydroxamic acid.

The inhibitory activity of a new peptidyl collagenase inhibitor, FN-439 or tetrapeptidyl hydroxamic acid (H2N-C6H4-CO-Gly-L-Pro-D-Leu-D-Ala-NHOH), was determined against vertebrate collagenases derived from human fibroblast, human polymorphonuclear leukocyte (PMN) and tadpole skin. In addition, the effect of FN-439 in inhibiting corneal ulceration was also investigated with alkali-burned rabbit corneas. FN-439 can block the active site of collagenase, and hydroxamic acid can chelate Zn2+ which is essential for collagenase activity.

Mitochondrial induction of adult T cell leukemia derived factor (ADF/hTx) after oxidative stresses in retinal pigment epithelial cells.

Purpose: Adult T cell leukemia derived factor (ADF) is a human homologue of thioredoxin (hTx), which exhibits scavenging activity with reactive oxygen intermediates. In their previous study, the authors found that after transient retinal ischemia, the expression of thioredoxin in rat retinal pigment epithelium (RPE) layer increased markedly. The present investigation is to determine intracellular ADF localization in RPE after transient ischemia and in cultured human RPE cells after oxidative insult by H2O2.

Re-evaluation of the colorimetric assay for cytidine deaminase activity.

This study re-evaluated the colorimetric assay for cytidine deaminase (CTD), and showed that the optimum conditions were pH 7.5, 37 degrees C, and up to 24 h. In addition, this method was found to require protein precipitation.

Morphologic and chromosomal study of a human retinal pigment epithelial cell line.

A spontaneously established cell line of human retinal pigment epithelium (RPE) was investigated morphologically and studied by chromosomal analysis. Even after the 100th passage, cultured cells maintained epithelioid morphology, and had numerous microvilli and membrane-bound small dense bodies which looked like lysosomes. Abundant rough-surfaced endoplasmic reticulum and mitochondria were observed in the cytoplasm, suggesting that these cells were metabolically active.