Quantitative analysis of three-dimensional fibrillar collagen microstructure within the normal, aged and glaucomatous human optic nerve head.

H J Jones,M J Girard,J E Morgan,N White,J Albon,M P Fautsch,C R Ethier

doi:10.1098/rsif.2015.0066

Abstract

The aim of this study was to quantify connective tissue fibre orientation and alignment in young, old and glaucomatous human optic nerve heads (ONH) to understand ONH microstructure and predisposition to glaucomatous optic neuropathy. Transverse (seven healthy, three glaucomatous) and longitudinal (14 healthy) human ONH cryosections were imaged by both second harmonic generation microscopy and small angle light scattering (SALS) in order to quantify preferred fibre orientation (PFO) and degree of fibre alignment (DOFA). DOFA was highest within the peripapillary sclera (ppsclera), with relatively low values in the lamina cribrosa (LC). Elderly ppsclera DOFA was higher than that in young ppsclera (p < 0.00007), and generally higher than in glaucoma ppsclera. In all LCs, a majority of fibres had preferential orientation horizontally across the nasal–temporal axis. In all glaucomatous LCs, PFO was significantly different from controls in a minimum of seven out of 12 LC regions (p < 0.05). Additionally, higher fibre alignment was observed in the glaucomatous inferior–temporal LC (p < 0.017). The differences between young and elderly ONH fibre alignment within regions suggest that age-related microstructural changes occur within the structure. The additional differences in fibre alignment observed within the glaucomatous LC may reflect an inherent susceptibility to glaucomatous optic neuropathy, or may be a consequence of ONH remodelling and/or collapse.

Highlights

Glaucoma is a multifactorial disease in which vascular and biomechanical mechanisms, in various combinations, have been proposed as important causes of retinal ganglion cell (RGC) axon death [1,2,3,4,5]
Recent studies have revealed the dynamic nature of glaucomatous optic neuropathy in which cells within the optic nerve head (ONH) are activated to respond to changes in their biomechanical and nutritional environment [4,5,6,7,8,9]
While previous studies have quantified ONH collagen fibre microstructure [15,17,31,32,37], this study is the first to quantify it as a function of age and glaucoma, simultaneously in both the lamina cribrosa (LC) and ppsclera of human eyes

Summary

Introduction

Glaucoma is a multifactorial disease in which vascular and biomechanical mechanisms, in various combinations, have been proposed as important causes of retinal ganglion cell (RGC) axon death [1,2,3,4,5]. While age and intraocular pressure (IOP) remain the major risk factors, the observation that a high IOP is not always required for the initiation of glaucomatous damage raises the possibility that some aspects of ONH structure may predispose some eyes to RGC axon damage. The lamina cribrosa (LC) is an important structural element in the ONH of the human eye and is most likely the site of RGC axonal damage in glaucoma [10], the second most common cause of bilateral irreversible blindness worldwide [11]. The collapse, compression and rearrangement of the LC connective tissue beams is accompanied by RGC axon death and vision loss [1,12]

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Methods

Conclusion