Eyes on the Complement System at the Third International Biennial Symposium on AMD 

Drawing nearly 250 clinicians, researchers, trainees, and industry representatives from around the world, the Third International Biennial Symposium on AMD, which was held October 24–25, 2014 and co-chaired by Chief and Chair of Ophthalmology, Joan Miller, MD, FARVO, and AMD Center of Excellence co-directors Patricia D’Amore, PhD, MBA, FARVO and Ivana Kim, MD, had special significance because it followed the 2014 António Champalimaud Vision Award, which recognized the development of antiangiogenic therapies for AMD and other retinal diseases. Five members of the HMS Department of Ophthalmology were among the seven Champalimaud Laureates who identified vascular endothelial growth factor (VEGF) as a therapeutic target.

The symposium showcased research from diverse disciplines to increase the understanding of AMD pathogenesis and identify new therapeutic strategies. Leaders from the fields of inflammation, neuroprotection, neurodegenerative disorders, and pathology joined experts in ophthalmology and vision research for a fervent, cross-disciplinary interchange of innovative concepts and investigative avenues. Talks were organized into sessions by topic, and each session concluded with a panel discussion composed of the session presenters and additional selected participants.

Reflecting the dynamic field of AMD research, symposium topics have evolved remarkably since the first symposium began in 2010. In the original symposium, the complement system of innate immunity was a major topic of discussion, catalyzed by a flurry of genetic studies that linked several complement-related genes with AMD risk. Although lipid metabolism largely dominated the 2nd symposium in 2012, the spotlight was “back on the complement bandwagon,” joked Robert D’Amato, MD, PhD, referring to the ongoing scrutiny of the complement system and clinical trials of complement-targeting therapies for AMD.

Additional immune-related topics included inflammasome activation and cellular modulators such as macrophages and mast cells. Other cross-disciplinary topics included oxidative stress and non-coding RNAs as biomarkers and therapeutic targets in AMD. Researchers also presented data on mechanisms of photoreceptor death and early-phase clinical investigation of stem cell therapy for the atrophic or “dry” form of AMD.

The field of AMD has also progressed beyond gene association studies. Efforts are underway to clarify the phenotypic outcomes of specific genotypes, and to elucidate the biological implications of gene variants. Besides the well-known effects on gene transcription and mRNA translation, novel repercussions of gene mutations (including “silent” polymorphisms) were discussed—such as altered protein translation rate and its impact on protein conformation and stability.