MFGE8 does not influence chorio-retinal homeostasis or choroidal neovascularization in vivo

Purpose: Milk fat globule-epidermal growth factor-factor VIII (MFGE8) is necessary for diurnal outer segment phagocytosis and promotes VEGF-dependent neovascularization. The prevalence of two single nucleotide polymorphisms (SNP) in MFGE8 was studied in two exsudative or “wet” Age-related Macular Degeneration (AMD) groups and two corresponding control groups. We studied the effect of MFGE8 deficiency on retinal homeostasis with age and on choroidal neovascularization (CNV) in mice. Methods: The distribution of the SNP (rs4945 and rs1878326) of MFGE8 was analyzed in two groups of patients with “wet” AMD and their age-matched controls from Germany and France. MFGE8-expressing cells were identified in Mfge8+/− mice expressing ß-galactosidase. Aged Mfge8+/− and Mfge8−/− mice were studied by funduscopy, histology, electron microscopy, scanning electron microscopy of vascular corrosion casts of the choroid, and after laser-induced CNV. Results: rs1878326 was associated with AMD in the French and German group. The Mfge8 promoter is highly active in photoreceptors but not in retinal pigment epithelium cells. Mfge8−/− mice did not differ from controls in terms of fundus appearance, photoreceptor cell layers, choroidal architecture or laser-induced CNV. In contrast, the Bruch's membrane (BM) was slightly but significantly thicker in Mfge8−/− mice as compared to controls. Conclusions: Despite a reproducible minor increase of rs1878326 in AMD patients and a very modest increase in BM in Mfge8−/− mice, our data suggests that MFGE8 dysfunction does not play a critical role in the pathogenesis of AMD

Integrating sustainable transport measures into the Clean Development Mechanism

While the number of projects under the Clean Development Mechanism (CDM) is expanding rapidly, there currently are relatively few transport projects in the global CDM portfolio. This article examines existing CDM transport projects and explores whether sectoral approaches to the CDM may provide a better framework for transport than the current project‐based CDM. We ask: Would a sectoral approach to the CDM promote the structural change and integrated policymaking needed to achieve sustainable transport policy, making it hence more desirable than the framework of the current project‐based CDM? We conclude that it is possible to design sectoral transport activities within clear project boundaries that fit into a framework of a programmatic or policy‐based CDM. Although we are able to ascertain that transport policy research yields several modelling tools to address the methodological requirements of the CDM, it becomes apparent that sectoral approaches will accentuate transport projects' problems regarding high complexity and related uncertainties. The CDM may need new rules to manage these risks. Nonetheless, sectoral approaches allow the scaling up of activities to a level that affects long‐term structural change

Anti-Tumor Necrosis Factor Alpha for Retinal Diseases: Current Knowledge and Future Concepts

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine produced by macrophages and T-cells. It plays an important role both in inflammation and apoptosis. In the eye, TNF-α appears to have a role in the pathogenesis of inflammatory, edematous, neovascular and neurodegenerative disorders. Several TNF-blocking drugs have been developed and approved, and are in clinical use for inflammatory diseases such as rheumatoid arthritis, psoriasis and ankylosing spondylitis. TNF-α blockers are widely used in ophthalmology as an off-label alternative to "traditional" immunosuppressive and immune-modulatory treatments in noninfectious uveitis. Preliminary studies suggest a positive effect of intravenously administered TNF-α blockers, mainly infliximab, for treating refractory diabetic macular edema and neovascular age-related macular degeneration. Unfortunately, much of the current data raises considerable safety concerns for intravitreal use of TNF-α inhibitors, in particular, intraocular inflammatory responses have been reported after intravitreal injection of infliximab. Results of dose-finding studies and humanized antibody or antibody fragments (e.g. adalimumab) are anticipated in the coming years; these will shed light on potential benefits and risks of local and systemic TNF-α blockers used for treatment of diseases of the retina and choroid