The two sides of cytokine signaling and glaucomatous optic neuropathy

The mechanistic study of glaucoma pathogenesis has shifted to seeking to understand the effects of immune responses on retinal ganglion cell damage and protection. Cytokines are the hormonal factors that mediate most of the biological effects in both the immune and nonimmune systems. CD4-expressing T helper cells are a major source of cytokine production and regulation. Type 1 helper T (Th1) cells are characterized by the production of proinflammatory cytokines such as interferon-gamma, interleukin (IL)-2, IL-12, IL-23, and tumor necrosis factor-alpha while type 2 helper T (Th2) cells are characterized by the production of IL-4, IL-5, IL-6, and IL-10. The balance of Th1/Th2 cytokine production influences many pathological processes and plays both causative and protective roles in neuron damages. Growing evidence indicates that imbalances of Th1/Th2 cytokine production are involved in neural damage or protection in many neurological diseases. In this review, we discuss the possible roles of Th1/Th2 cytokine production and imbalance of Th1/Th2 cytokines in retina, especially glaucomatous optic neuropathy

ACE as a Mechanosensor to Shear Stress Influences the Control of Its Own Regulation via Phosphorylation of Cytoplasmic Ser1270

Objectives: We tested whether angiotensin converting enzyme (ACE) and phosphorylation of Ser(1270) are involved in shear-stress (SS)-induced downregulation of the enzyme. Methods and Results: Western blotting analysis showed that SS (18 h, 15 dyn/cm(2)) decreases ACE expression and phosphorylation as well as p-JNK inhibition in human primary endothelial cells (EC). CHO cells expressing wild-type ACE (wt-ACE) also displayed SS-induced decrease in ACE and p-JNK. Moreover, SS decreased ACE promoter activity in wt-ACE, but had no effect in wild type CHO or CHO expressing ACE without either the extra-or the intracellular domains, and decreased less in CHO expressing a mutated ACE at Ser(1270) compared to wt-ACE (13 vs. 40%, respectively). The JNK inhibitor (SP600125, 18 h), in absence of SS, also decreased ACE promoter activity in wt-ACE. Finally, SS-induced inhibition of ACE expression and phosphorylation in EC was counteracted by simultaneous exposure to an ACE inhibitor. Conclusions: ACE displays a key role on its own downregulation in response to SS. This response requires both the extra- and the intracellular domains and ACE Ser(1270), consistent with the idea that the extracellular domain behaves as a mechanosensor while the cytoplasmic domain elicits the downstream intracellular signaling by phosphorylation on Ser(1270).Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[01/00009-0]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[03/14115-2]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[06/52053-7]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)[480120/2007-2

Neuroprotection in glaucoma: a model for neuroprotection in optic neuropathies

Purpose of review: Efforts to discover modalities and pathophysiologies that might afford successful neurorescue, neurorestoration, and neuroprotection of cells of the central nervous system have focused on processes that affect the central nervous system proper, that is, the brain. Often overlooked in the search for neural protection is the fact that the mammalian optic nerve behaves in many ways as an integral part of the central nervous system. As such, the eye-the optic nerve and retina-affords an ideal clinical model for neuroprotection and neuroprotective agents. Glaucomatous optic neuropathy is the most prevalent of all adult optic neuropathies, and offers an ideal primate and lower mammalian animal model for investigations of neuroprotection. Recent findings: This is especially compelling because while recent studies in glaucoma have shown reduction of intraocular pressure (IOP) to be an effective modality in the treatment of glaucomatous opt c neuropathy, not all patients respond to or can achieve meaningful IOP reductions. Therefore much attention has now been focused on neuroprotection as a strategy in therapies for glaucomatous optic neuropathy as a means of preserving retinal ganglion cells and their axonal projections. Summary: This review discusses the latest studies on various mechanisms of neuroprotection in the treatment of glaucomatous optic neuropathy. © 2003 Lippincott Williams & Wilkins

Long-lasting and controlled antioxidant property of immobilized gold nanoparticles for intelligent packaging

International audienceThe development of new packaging able to preserve sensitive biomolecules against oxidative stress is an important field. Several studies refer to antioxidant properties carried out by colloidal gold nanoparticles (AuNP). Herein, the purpose was to check whether this property is preserved when AuNP are immobilized on a glass support. After nanostructured film preparation, the physicochemical characterization proved that AuNP were well-individualized in the films with a high density of immobilization. Two radicals: ABTS•+ and DPPH• were used to investigate their antioxidant capacity. The results showed that immobilized AuNP had a preserved antioxidant capacity characterized by a different kinetic: more controlled and more prolonged but with the same efficiency (vs the same quantity of colloidal AuNP). The AuNP films demonstrated a capacity to prevent from degradation a molecule containing a thiol function. A 10-fold increase of N-acetylcysteine half-life was measured using the immobilized AuNP, highlighting the interest of the developed and adaptable support