No abstract

Background: Autophagy is a conserved process of lysosome-mediated intracellular degradation. Results: Dysregulation of autophagy is associated with retinal cell death by all-trans-retinal and by light exposure. Conclusion: Autophagy protects the retina from light-induced retinal degeneration. Significance: Dynamic autophagy regulation may influence retinal cell survival under stress and disease conditions.

A systems pharmacological approach that capitalizes on the characterization of intracellular signaling networks can transform our understanding of human diseases and lead to therapy development. Here, we applied this strategy to identify pharmacological targets for the treatment of Stargardt disease, a severe juvenile form of macular degeneration. Diverse GPCRs have previously been implicated in neuronal cell survival, and crosstalk between GPCR signaling pathways represents an unexplored avenue for pharmacological intervention. We focused on this receptor family for potential therapeutic interventions in macular disease. Complete transcriptomes of mouse and human samples were analyzed to assess the expression of GPCRs in the retina. Focusing on adrenergic (AR) and serotonin (5-HT) receptors, we found that adrenoceptor α 2C (Adra2c) and serotonin receptor 2a (Htr2a) were the most highly expressed. Using a mouse model of Stargardt disease, we found that pharmacological interventions that targeted both GPCR signaling pathways and adenylate cyclases (ACs) improved photoreceptor cell survival, preserved photoreceptor function, and attenuated the accumulation of pathological fluorescent deposits in the retina. These findings demonstrate a strategy for the identification of new drug candidates and FDA-approved drugs for the treatment of monogenic and complex diseases.

The wide-angle OCTA seems to be clinically useful for the detection of NPAs or NV.

Intravitreal injection of bevacizumab decreased the VEGF concentration in the treated eyes for at least 4 weeks and had no or a minimal effect on the untreated fellow eyes.

To study the concentration of vascular endothelial growth factor in the aqueous humor before and after intravitreal injection of bevacizumab in eyes with proliferative diabetic retinopathy. Methods: In this prospective, interventional case series, 1.25 mg of bevacizumab was injected into the vitreous cavity as preoperative adjunctive therapy 1 week before pars plana vitrectomy to treat proliferative diabetic retinopathy in 18 eyes in 18 patients. Aqueous humor samples were obtained just before intravitreal injection of bevacizumab and just before vitrectomy 1 week after the injection. Aqueous humor samples also were obtained in patients with cataract without diabetes mellitus (control group). The vascular endothelial growth factor concentration in the aqueous humor was measured using an enzyme-linked immunosorbent assay. Results: Vascular endothelial growth factor concentration in the aqueous humor ranged from 146 to 676 pg/mL (mean±SD, 326±125 pg/mL) before intravitreal injection of bevacizumab and decreased to less than 31 pg/mL (P Ͻ.001) in all eyes 1 week after injection. Intravitreal bevacizumab therapy caused no adverse events. The concentrations in the control group ranged from 80 to 218 pg/mL (mean±SD, 146±40 pg/mL). Conclusion: Intravitreal injections of bevacizumab resulted in a substantial decrease in vascular endothelial growth factor in the aqueous humor.

Abstract.We examined cytotoxic effects of nicotine/tar-free cigarette smoke extract (CSE) on C6 glioma cells. The CSE induced plasma membrane damage (determined by lactate dehydrogenase leakage and propidium iodide uptake) and cell apoptosis {determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] reduction activity and DNA fragmentation}. The cytotoxic activity decayed with a half-life of approximately 2 h at 37°C, and it was abolished by N-acetyl-L-cysteine and reduced glutathione. The membrane damage was prevented by catalase and edaravone (a scavenger of• OH) but not by superoxide dismutase, indicating involvement of • OH. In contrast, the CSE-induced cell apoptosis was resistant to edaravone and induced by authentic H 2 O 2 or O 2 − generated by the xanthine/xanthine oxidase system, indicating involvement of H 2 O 2 or O 2 − in cell apoptosis. Diphenyleneiodonium [NADPH oxidase (NOX) inhibitor] and bisindolylmaleimide I [BIS I, protein kinase C (PKC) inhibitor] abolished membrane damage, whereas they partially inhibited apoptosis. These results demonstrate that 1) a stable component(s) in the CSE activates PKC, which stimulates NOX to generate reactive oxygen species (ROS), causing membrane damage and apoptosis; 2) different ROS are responsible for membrane damage and apoptosis; and 3) part of the apoptosis is caused by oxidants independently of PKC and NOX.[Supplementary methods and Figure: available only at http://dx

Cirrus showed better reliability than Stratus. Using SD-OCT, the macula was 60-microm thicker than when measured with TD-OCT. Attention should be given to comparing data obtained using different OCT machines.