Effects of scleral collagen crosslinking with different carbohydrate on chemical bond and ultrastructure of rabbit sclera: Future treatment for myopia progression

PLoS One. 2019 May 13;14(5):e0216425. doi: 10.1371/journal.pone.0216425. eCollection 2019.

Abstract

Background: Myopia is the most common ocular disorder and is mainly caused by axial elongation of the sclera. If the stiffness of sclera increased, it can inhibit myopia progression. The aim of this study is to compare the effect of the collagen crosslinking with different types and concentrations of carbohydrates on chemical bond and ultrastructural change of rabbit sclera.

Methods: Nine New Zealand white rabbits were treated with five, sequential sub-Tenon injections of 0.15 mL solutions of ribose, sucrose, and glycogen of 0.1, 0.2 and 0.4 M concentration at the right eye over 14 days. Ten weeks after the last injection, the rabbits were sacrificed and chemical bond and ultrastructural changes were compared with those of the untreated left sclera using Raman spectroscopy, atomic force microscopy (AFM), and histology.

Results: Raman spectroscopy of the control and cross-linked rabbit sclera tissue revealed different types of collagen interactions. Raman shift of 919 cm-1 (C-C stretching and vibration of the proline ring in collagen) was the highest in ribose, followed by sucrose and glycogen. Total energy intensity was also highest in ribose, followed by sucrose and glycogen, and showed a tendency to increase at higher concentrations. AFM revealed interlocking arrangements of collagen fibrils. The collagen fibril diameter was 105.6 ± 21.2 nm, 109.4 ± 28.8 nm, 113.1 ± 30.8 nm and 137.6 ± 25.3 nm for control group, 0.4 M glycogen, sucrose, and ribose, respectively. Histology indicated increased density of the collagen bundle and no increase in inflammatory cell recruitment compared to control at high concentrations of ribose.

Conclusions: Scleral crosslinking using glycation increased the scleral biomechanical rigidity and these results were particularly pronounced in ribose. Scleral crosslinking using glycation may be a promising method for inhibiting high myopia progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen / metabolism*
  • Disease Models, Animal
  • Glycogen / metabolism*
  • Glycosylation
  • Myopia, Degenerative* / metabolism
  • Myopia, Degenerative* / pathology
  • Rabbits
  • Ribose / metabolism*
  • Sclera* / metabolism
  • Sclera* / ultrastructure
  • Sucrose / metabolism*

Substances

  • Sucrose
  • Ribose
  • Glycogen
  • Collagen

Grants and funding

This research was supported by the National Research Foundation of Korea (NRF) funded by 2018M3A9E8078812 to TGK and 2017R1A2B4002765 to SC. There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.