Structure of abnormal molecular assemblies (collagen VI) associated with human full thickness macular holes

Transversely banded deposits with an approximately 100-nm periodicity have been seen in association with a number of eye pathologies (e.g., age-relate d macular degeneration). Recently such aggregates have also been discovered in the cortical vitreous of a patient suffering from full thickness macula r holes. The aggregates in the vitreous were of sufficient size and regular ity for us to attempt 3D ultrastructural studies in the electron microscope . The molecules forming this aggregate pack in a centered tetragonal unit c ell of dimensions similar to 26 x 26 x 180 nm. A real-space (r-weighted bac k projection) 3D reconstruction was computed. The aggregate is discussed in terms of its possible protein constituents. Collagen VI has been singled o ut as the most likely protein to form the aggregate. Two alternative models for the molecular packing are proposed, comprising aggregates of molecular tetramers or octamers, Understanding the structure of these abnormal bande d deposits in the eye should help to throw light on the pathophysiological mechanisms of the diseases, including age-related macular degeneration, in which they occur. (C) 2000 Academic Press.