The Structural Order of Crystallin Proteins During Early Human Lens Development

TL;DR

This study examines how crystallin proteins in the human lens organize during early development, showing changes in spacing and order over time.

Contribution

The paper provides new insights into the structural changes of crystallin proteins in the human lens during development using small-angle X-ray scattering.

Findings

Crystallin proteins in the lens center become more compact as development progresses.

Spatial order of crystallin proteins decreases over time, as measured by coherence distance.

The lens periphery consistently shows higher spacing and spatial order compared to the center.

Abstract

To study the structural arrangement of crystallin proteins in the human lens during development.

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.

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.

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.

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