A microstructural basis for nonlinear effects of IOP on the lamina cribrosa and sclera

Abstract

 

Purpose

 

The LC and sclera stiffen as IOP increases. The underlying causes are unclear, but are thought to be due to collagen fiber uncrimping with IOP. Our goal was to measure the waviness of the fibers of the LC and sclera and determine their uncrimping with IOP elevation

 

Methods

 

23 sheep eyes were fixed in 10% formalin at various IOPs (0, 10, 15, 20, and 50mmHg), with at least 1 eye at each pressure. The posterior poles were cryosectioned coronally (30 µm), and at least 3 sections through the LC per eye were imaged using polarized light microscopy. Images were analyzed for waviness by calculating the SD of the collagen fiber orientation in manually marked lines (Sigal IA, et al. IOVS 2013;54: E-Abstract 3158). In the LC, the waviness of every collagen beam was measured. In the sclera, at least 900 measurements were made per eye (Fig 1). We analyzed the waviness using mixed effect models, accounting for correlations between measurements from the same sections, eyes and animals. Using the waviness at 50mmHg we defined tissue-specific thresholds to determine the fraction of uncrimped fibers

 

Results

 

At every IOP waviness was lower in the LC than in the sclera (p<0.001, Fig 2). As IOP increased, waviness decreased in both the LC and sclera (p<0.001), and faster at lower IOPs than at higher IOPs (p<0.001). At all IOPs, except 15mmHg, a larger fraction of sclera than LC fibers were uncrimped (Fig 2). At 15 mmHg LC and sclera had the same fraction of uncrimped fibers (74%). At lower IOPs, few sclera (57%), and even fewer LC (32%) fibers were uncrimped

 

Conclusions

 

The decrease in waviness with IOP and associated fiber recruitment explain the macro-scale nonlinear behavior of the LC and sclera with IOP. The decrease in fraction of uncrimped LC fibers between 15 and 20mmHg may be a protective effect from sclera. We have demonstrated that fiber-level stretch and tissue-level recruitment can be detected directly using waviness. Decrease in waviness indicates LC regions under IOP-induced stretch and perhaps increased risk of neural tissue damage  

 

Example section, with yellow lines at the locations where collagen waviness was measured in the sclera and the blue line at the canal border

 

 

Effects of IOP on collagen waviness (top) and fraction of uncrimped fibers (bottom). As fibers are stretched with IOP, they uncrimp, decreasing in waviness. A fully uncrimped fiber bears considerably more load and is called recruited