Intravitreal anti-vascular endothelial growth factor therapy with bevacizumab for tuberous sclerosis with macular oedema

Purpose: To describe two patients with macular oedema secondary to tuberous sclerosis complex (TSC), who were treated with intravitreal bevacizumab injection. Methods: Interventional case reports. Bevacizumab 1.25 mg was injected into the vitreous of two patients with TSC-associated macular oedema / exudative retinal detachment. VEGF concentration in the vitreous fluid was measured by ELISA in one of these patients. Results: Case 1. 22-year-old woman with TSC was diagnosed as having multiple retinal hamartomas in both eyes. Eleven years later, the patient developed macular oedema with epiretinal membrane formation in the right eye. The patient underwent pars plana vitrectomy with retinal photocoagulation for retinal tumours. VEGF concentration in the vitreous fluid was high compared to that in patients without retinal vascular diseases. Recurrent macular oedema was resolved by intravitreal injection of bevacizumab. Case 2. 32-year-old woman with TSC-associated retinal hamartoma, temporally showing macular exudative retinal detachment, developed the neovascularization originated from the tumour. By intravitreal bevacizumab injection, the tumour size markedly reduced with regression of neovascularization. Conclusions: These results suggest that VEGF derived from retinal hamartomas causes macular oedema associated with TSC. Intravitreal injections of bevacizumab may be a useful therapeutic option for macular oedema secondary to TSC

Inhibition of nuclear factor-kappa B activation attenuates hydrogen peroxide-induced cytotoxicity in human lens epithelial cells

Aims: Hydrogen peroxide (H2O2) is the major oxidant involved in cataract formation. Lens epithelial cells have been suggested to be the first site of oxidative damage. The authors investigated the relationship between H2O2-induced cytotoxicity and activation of nuclear factor kappa B (NF-B) in human lens epithelial (HLE) cells. Methods: HLE B-3 cells were stimulated by various concentrations of H2O2 in the presence or absence of pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-B. H2O2-induced cytotoxicity was measured by lactate dehydrogenase cytotoxicity assay. Translocation of NF-B was examined by Western blot and immunocytochemistry using anti-p65 antibody. Results: H2O2-induced cytotoxicity increased in a concentration-dependent manner. PDTC treatment significantly suppressed the cytotoxicity induced by H2O2. After stimulated with H2O2, NF-B was found translocated from cytoplasm into the nuclei. PDTC treatment also inhibited the translocation of NF-B. Conclusions: NF-B signal pathway may be important in the development of H2O2-induced damage in HLE cells that is involved in cataractogenesis

Increase in macrophage migration inhibitory factor levels in lacrimal fluid of patients with severe atopic dermatitis

Background and aims of the study Atopic dermatitis is a chronic inflammatory skin disorder that often involves some ophthalmic features. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is associated with the generation of cell-mediated immune responses. Although serum MIF levels may be elevated in severe atopic dermatitis, the quantity of MIF in regional ocular fluid remains unknown. We measured MIF levels in tears (lacrimal fluid) of patients with atopic dermatitis. Patients and methods Tear samples were collected from 16 patients with atopic dermatitis, 10 patients with allergic conjunctivitis, and 15 healthy control subjects. The clinical severity of atopic dermatitis was evaluated according to the Scoring Atopic Dermatitis (SCORAD) index. The index was calculated by summing the following scores: extent criteria, intensity criteria, and subjective symptoms. Macrophage migration inhibitory factor levels were determined by a human MIF enzyme-linked immunosorbent assay. All comparisons were two-tailed, and P values <0.01 were considered as statistically significant. Results The mean MIF concentration in lacrimal fluid collected from healthy control subjects was 0.69±0.2 ng/ml. The mean tear MIF levels were 17.87±6.3 ng/ml in moderate-to-severe atopic dermatitis (SCORAD≥15, P=0.002), 0.93±0.08 ng/ml in mild atopic dermatitis (SCORAD<15), and 2.76±0.86 ng/ml in allergic conjunctivitis (P=0.008). Conclusions A proinflammatory cytokine MIF level was elevated in tears as well as serum in cases of severe atopic dermatitis. These results suggest that MIF may play an important role in the induction or enhancement of ophthalmic features related to severe atopic dermatitis

Captopril suppresses inflammation in endotoxin-induced uveitis in rats

Captopril is an inhibitor of angiotensin-converting enzyme (ACE) that is largely used in the treatment of cardiovascular diseases. Several previous studies have demonstrated that captopril exhibits a wide variety of biological activities, including an anti-inflammatory action, on which we focused our attention. The aim of the present study was to investigate the efficacy of captopril on endotoxin induced uveitis (EIU) in rats. We investigated its effect upon cellular infiltration and protein leakage, as well as on the concentration of tumor necrosis factor-α (TNF-α), nitric oxide (NO), prostaglandin E2 (PGE2), monocyte chemoattractant protein-1 (MCP-1) in the anterior chamber. In addition, we checked its effect on activation of nuclear factor kappa B (NF-κB) in iris and ciliary body (ICB) cells in vivo. EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). One hour after the LPS inoculation, either 1 mg/kg, 10 mg/kg or 100 mg/kg captopril were injected intravenously. 24 h later, the aqueous humor was collected from both eyes, and the number of infiltrating cells and protein concentration in the aqueous humor were determined. Levels of TNF-α, PGE2, NO and MCP-1 were determined by enzyme-linked immunosorbent assay. On some eyes, after enucleation, immunohistochemical staining with a monoclonal antibody against activated NF-κB was performed. Captopril treatment significantly decreased the inflammatory cells infiltration, the level of protein, concentrations of TNF-α, PGE2, NO and MCP-1 in the aqueous humor. The number of activated NF-κB-positive cells was lower in ICB of the rats treated with captopril 3 h after the LPS injection. The present results indicate that captopril suppresses the inflammation in EIU by inhibiting the NF-κB-dependent pathway and the subsequent production of pro-inflammatory mediators

Immunolocalization of cyclin D1 in the developing lens of c-maf -/- mice

The maf gene encodes a transcription factor protein containing a typical basic/leucine zipper domain structure, a motif for protein dimerization and DNA binding. It has been demonstrated that maf family genes have important roles in embryonic development and cellular differentiation. In this study, localization of cyclin D1, one of the cell cycle-related molecules, was examined immunohistochemically in developing lens cells of c-maf knockout (-/-) mice. At embryonic day 14 in wild-type mice, lens cells consisted of round epithelial cells in a single layer and regularly arranged elongated lens cells, indicating primary lens fiber cells. Cyclin D1-positive nuclei were observed in the lens epithelial cells, whereas cyclin D1 was not detected in the primary lens fiber cells. In c-maf -/- mice, a variety of round epithelial cells were located in the anterior and posterior lens. Many cyclin D1-positive nuclei were observed in lens epithelial cells as well as posterior lens cells. These results are consistent with c-maf playing a role in the regulation of cyclin D1 in developing lens cells

Expression of thymidine phosphorylase in choroidal malignant melanoma associated with neovascular glaucoma.

Reported herein is a case of 62-year-old man who complained of blurred vision and ocular pain in his right eye. The patient was diagnosed with choroidal melanoma complicated by neovascular glaucoma (NVG) and total retinal detachment, and he underwent enucleation of the eye. The isolated tumor was 2.5 × 2.5 cm in size. It was accompanied by intratumoral calcification, and consisted of epithelioid and spindle melanoma cells. There were a variety of microvessels in the stroma of the iris. The expression of thymidine phosphorylase (dThdPase), an angiogenic factor, was examined immunohistochemically. Cytoplasmic immunoreactivity for dThdPase was more prominent in the epithelioid cells than in spindle tumor cells. Another case of choroidal melanoma without NVG had less marked immunoreactivity. These results suggest that the production of dThdPase by melanoma cells correlates with the pathogenesis of NVG