Tag Archives: Tucker Williamson

A Targeted Inhibitor Of The Alternative Complement Pathway Accelerates Recovery From Smoke-Induced Ocular Injury

We have a new publication out, A Targeted Inhibitor Of The Alternative Complement Pathway Accelerates Recovery From Smoke-Induced Ocular Injury authored by Alex Woodell, Bryan W. Jones, Tucker Williamson, Gloriane Schnabolk, Stephen Tomlinson, Carl Atkinson and Bärbel Rohrer.

Abstract:
PURPOSE. Morphological and genetic evidence exists that an overactive complement system driven by the complement alternative pathway (CAP) is involved in pathogenesis of age- related macular degeneration (AMD). Smoking is the only modifiable risk factor for AMD. As we have shown that smoke-related ocular pathology can be prevented in mice that lack an essential activator of CAP, we ask here whether this pathology can be reversed by increasing inhibition in CAP.

METHODS. Mice were exposed to either cigarette smoke (CS) or filtered air (6 hours/day, 5 days/week, 6 months). Smoke-exposed animals were then treated with the CAP inhibitor (CR2-fH) or vehicle control (PBS) for 3 months. Spatial frequency and contrast sensitivity were assessed by optokinetic response paradigms at 6 and 9 months; additional readouts included assessment of retinal morphology by electron microscopy (EM) and gene expression analysis by quantitative PCR.

RESULTS. The CS mice treated with CR2-fH showed significant improvement in contrast threshold compared to PBS-treated mice, whereas spatial frequency was unaffected by CS or pharmacological intervention. Treatment with CR2-fH in CS animals reversed thinning of the retina observed in PBS-treated mice as analyzed by spectral-domain optical coherence tomography, and reversed most morphological changes in RPE and Bruch’s membrane seen in CS animals by EM.

CONCLUSIONS. Taken together, these findings suggest that CAP inhibitors not only prevent, but have the potential to accelerate, the clearance of complement-mediated ocular injury. Improving our understanding of the regulation of the CAP pathway is paramount to developing novel treatment approaches for AMD.

The Alternative Complement Pathway Deficiency Amerliorates Chronic Smoked-Induced Functional And Morphological Ocular Injury

Alex Woodell, Beth Coughlin, Kannan Kunchithapautham, Sarah Casey, Tucker Williamson, W. Drew Ferrell,  Carl Atkinson, Bryan Jones and Baerbel Rohrer have a new manuscript out, The Alternative Complement Pathway Deficiency Amerliorates Chronic Smoked-Induced Functional And Morphological Ocular Injury in PLOS One.

The short story is: Don’t smoke.  But then you knew that.  Where this paper contributes is that it provides clear findings that show ocular pathologies generated by cigarette smoke are dependent upon activation of the immune system, in particular complement and the alternative pathway which are critical findings in the treatment of AMD.