The Structural Order of Crystallin Proteins During Early Human Lens Development.

Purpose: To study the structural arrangement of crystallin proteins in the human lens during development. Methods: Fetal human lenses were acquired from the UK Human Developmental Biology Resource and examined at four developmental stages; postconception weeks (pcw) 8 to 9 (n = 5), 12 to 13 (n = 3), 16 to 17 (n = 6), and 20 to 21 (n = 3). Small-angle X-ray scattering patterns were obtained as raster scans across the entirety of each lens using a 0.1 nm-wavelength, synchrotron X-ray beam measuring 200 × 150 µm at the specimen. Analysis of each small-angle X-ray scattering pattern provided a measure of the average nearest neighbor spacing and the extent of spatial order in the crystallin protein array. Results: Crystallins in the lens center became compacted as development progressed, with the average spacing measuring 19.9 nm at 8 to 9 pcw, 19.6 nm at 12 to 13 pcw, 18.7 nm at 16 to 17 pcw, and 17.7 nm at 20 to 21 pcw. The spatial order of the crystallin proteins in the lens center also decreased with time as indicated by a parameter called the coherence distance, which measured 26.9 nm at 8 to 9 pcw, 24.7 nm at 12 to 13 pcw, 24.6 nm at 16 to 17 pcw, and 24.9 nm at 20 to 21 pcw. Spacing and spatial order were consistently higher at the lens periphery, compared with the center, at all developmental stages studied. Conclusions: Spatiotemporal modifications in the array of crystallin proteins occur as the human lens develops. These are perhaps reflective of a shift in the relative proportions of crystallin subtypes present and have potential implications for the lens's developing refractive index.