This multicenter retrospective study was conducted to evaluate the 1-year treatment outcome of photodynamic therapy (PDT) combined with anti-vascular endothelial growth factor (VEGF) therapy for pachychoroid neovasculopathy (PNV). A total of 42 eyes of 42 patients with treatment-naïve PNV who were treated with PDT combined with intravitreal injections of an anti-VEGF agent (ranibizumab or aflibercept) for 1 year. All eyes showed exudative and/or hemorrhagic changes that affected the fovea at baseline.
View Article and Find Full Text PDFPurpose: Intravitreal injection of anti-VEGF drugs has become standard therapy for patients with exudative age-related macular degeneration (AMD). However, some patients do not exhibit sufficient response to the drugs for suppression of choroidal neovascularization activity. We investigated the efficacy of switchback from ranibizumab to aflibercept in patients with AMD who could not achieve further benefit beyond initial therapy of aflibercept injection.
View Article and Find Full Text PDFPurpose: To evaluate a modified treat-and-extend (TAE) regimen of intravitreal aflibercept injection (IAI) for treatment-naïve patients with neovascular age-related macular degeneration (AMD).
Methods: Thirty-six eyes (36 patients) treated with the modified TAE regimen were evaluated at 12 months retrospectively. The modified TAE regimen consisted of three steps: 1) an induction phase, during which patients were treated with ≥ 3-monthly IAIs until exudative activity disappeared, 2) an observation phase, during which patients were monitored until exudative activity appeared, and 3) a TAE phase, for which the initial treatment interval was determined based on the disease recurrence interval, followed by treatment intervals changing by 2 weeks.
Retinitis pigmentosa is a group of diseases in which one of hundreds of mutations causes death of rod photoreceptor cells and then cones gradually die from oxidative damage. As different mutations cause rod cell death by different mechanisms, mutation-specific treatments are needed. Another approach is to use a neurotrophic factor to promote photoreceptor survival regardless of the mechanism of cell death, and previous studies have demonstrated encouraging short-term results with gene transfer of glial cell line-derived neurotrophic factor (GDNF).
View Article and Find Full Text PDFMüller glia are the primary glial subtype in the retina and perform a wide range of physiological tasks in support of retinal function, but little is known about the transcriptional network that maintains these cells in their differentiated state. We report that selective deletion of the LIM homeodomain transcription factor Lhx2 from mature Müller glia leads to the induction of reactive retinal gliosis in the absence of injury. Furthermore, Lhx2 expression is also down-regulated in Prph2(Rd2/Rd2) animals immediately before the onset of reactive gliosis.
View Article and Find Full Text PDFObjective: This study compared the effects of intraocular injections of ranibizumab (RBZ) and bevacizumab (BVZ) in transgenic mouse models in which human vascular endothelial growth factor (VEGF) causes subretinal neovascularization (NV) or exudative retinal detachment.
Design: Randomized trials in animal models.
Participants: Transgenic mice in which the rhodopsin promoter drives expression of human VEGF in photoreceptors (rho/VEGF mice) and double transgenic mice with doxycycline-inducible expression of human VEGF in photoreceptors (Tet/opsin/VEGF mice).
Retinitis pigmentosa (RP) is a collection of diseases in which rod photoreceptors die from a variety of mutations. After rods die, the level of tissue oxygen in the outer retina becomes elevated and there is progressive oxidative damage to cones that ultimately triggers apoptosis. In this study, we investigated the hypothesis that NADPH oxidase (Nox) and/or xanthine oxidase serve as critical intermediaries between increased tissue oxygen and the generation of excessive reactive oxygen species that cause oxidative damage to cones.
View Article and Find Full Text PDFBackground: There have been no previous studies of the effects of poly(ADP-ribose) polymerase (PARP) inhibitors on N-methyl-N-nitrosourea (MNU)-induced cataractogenesis in rats.
Materials And Methods: A single intraperitoneal injection of 70 mg/kg MNU was administered to 15-day-old male and female Sprague-Dawley rats. In Experiment 1, rats were then subcutaneously injected with 1000 mg/kg nicotinamide either once or 3 times at 1-week intervals.
An autopsy case of pseudoxanthoma elasticum is reported. A Japanese female patient complained of yellow papules on the neck, precordium, and axilla, beginning at 54 years of age. When the patient was 58 years old, in response to her visual disturbance a funduscopic examination was performed, revealing angioid streaks, and skin biopsy identified a characteristic pseudoxanthoma elasticum (PXE) lesion.
View Article and Find Full Text PDFWe examined the effects of short-term estrogen and progesterone treatment mimicking pregnancy in aged female Lewis rats on the development of N-methyl-N-nitrosourea (MNU)-induced mammary carcinoma. Rats were administered a single intraperitoneal injection of 20 mg/kg MNU at 7 weeks of age and half of those rats were administered a subcutaneously implanted 21-day release pellet containing 0.5 mg 17beta-estradiol and 32.
View Article and Find Full Text PDFDesminopathy is a familial or sporadic skeletal and cardiac muscular dystrophy caused by mutation in the desmin gene. Desmin-reactive deposits in the affected muscles are the morphological hallmarks of this disease. Herein is reported an autopsy case of a 57-year-old Japanese man with adult-onset skeletal muscle weakness and atrioventricular (A-V) conducting block, with a missense A337P mutation in exon 5 of the desmin gene.
View Article and Find Full Text PDFThe activation of poly (ADP-ribose) polymerase (PARP) plays a pivotal role in mediating N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell apoptosis. We examined the retinoprotective effects of the PARP inhibitor 3-aminobenzamide (3-AB) against MNU-induced retinal damage in relation to dose and timing of prescription, and the involvement of the transcription factor nuclear factor (NF)-kappaB. Female Sprague-Dawley rats were intraperitoneally injected with 60 mg/kg MNU at 50 days of age, and were then immediately given a subcutaneous injection of 0, 1, 5, 10, 30 or 50 mg/kg of 3-AB, or were injected with 50 mg/kg 3-AB 12h before, concurrently, or 4, 6 or 12h after MNU.
View Article and Find Full Text PDFZeranol (alpha-zearalanol) is a metabolite of the mycoestrogen zearalenone, and is used as a growth promoter of livestock due to its strong estrogenic activity. In the present study, we investigated the effects of zeranol on the growth of estrogen receptor (ER)-positive and -negative human breast carcinoma cells in vitro, and the molecules involved. At low concentrations, zeranol accelerated the growth of ER-positive MCF-7 and KPL-1 human breast carcinoma cells, but did not affect the growth of ER-negative MDA-MB-231 cells.
View Article and Find Full Text PDFAn autopsy case of a 19-year-old male Japanese student with a primary mixed choriocarcinoma and mature teratoma in the thymic region is reported. The patient died 7 days after he first noticed fever and dyspnea. On autopsy, an anterior mediastinal mass was found to be in contact with the thymic gland.
View Article and Find Full Text PDFBackground: The effects of differences in gender and gonadal status on the occurrence of N-methyl-N-nitrosourea (MNU)-induced cataract and retinopathy were studied using ovary-intact, ovariectomized, testis-intact and testectomized Lewis rats.
Materials And Methods: Castration was performed at 36 days of age, 50 mg/kg MNU was administered intraperitoneally at 50 days of age, and lens and retinal changes were evaluated at 260 days of age (210 days after MNU injection).
Results: Although there was little difference in the incidence of cataract and retinopathy among the groups, ovary-intact rats had a significantly higher cataract index and retinal damage ratio (both are indicators of disease severity) than ovariectomized rats and testis-intact rats, respectively.
Nicotinamide (NAM) blocks N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell apoptosis in rats, though the underlying molecular mechanisms remain unclear. Activation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) in response to DNA damage plays a pivotal role in apoptosis. Thus, the role of NAM in the regulation of PARP and Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) was investigated by Western blot analyses.
View Article and Find Full Text PDFPatients with primary open-angle glaucoma (POAG) were dosed twice-daily with 0.5% timolol maleate for 2 years, followed by 2 years of twice-daily dosing with 0.5% betaxolol hydrochloride.
View Article and Find Full Text PDFThe accumulation of DNA damages by environmental stresses is represented by the steady state level of single strand breaks (SSBs) and double strand breaks (DSBs). Terminal deoxynucleotidyl transferase (TdT) mediated end labeling is suitable in detecting DSBs, but is unsuitable for SSBs due to its catalyzing characteristics. However, the sensitivity of TdT to detect SSBs may be significantly improved by first denaturing the double strands and expose all the DNA nicks as potential substrates for TdT.
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