Biomechanical aspects of axonal damage in glaucoma: A brief review

Abstract

The biomechanical environment within the optic nerve head (ONH) is complex and is likely directly involved in the loss of retinal ganglion cells (RGCs) in glaucoma. Unfortunately, our understanding of this process is poor. Here we describe factors that influence ONH biomechanics, including ONH connective tissue microarchitecture and anatomy; intraocular pressure (IOP); and cerebrospinal fluid pressure (CSFp). We note that connective tissue factors can vary significantly from one individual to the next, as well as regionally within an eye, and that the understanding of ONH biomechanics is hindered by anatomical differences between small-animal models of glaucoma (rats and mice) and humans. Other challenges of using animal models of glaucoma to study the role of biomechanics include the complexity of assessing the degree of glaucomatous progression; and inadequate tools for monitoring and consistently elevating IOP in animal models. We conclude with a consideration of important open research questions/challenges in this area, including: (i) Creating a systems biology description of the ONH; (ii) addressing the role of astrocyte connective tissue remodeling and reactivity in glaucoma; (iii) providing a better characterization of ONH astrocytes and non-astrocytic constituent cells; (iv) better understanding the role of ONH astrocyte phagocytosis, proliferation and death; (v) collecting gene expression and phenotype data on a larger, more coordinated scale; and (vi) developing an implantable IOP sensor.

When is a control not a control? Reactive microglia occur throughout the control contralateral visual pathway in experimental glaucoma

“…Following periods of OHT, we identified global eye expansion as a feature of the paramagnetic bead model. While this is not a feature of adult glaucoma, it occurs in congenital glaucoma where the sclera is less rigid and more elastic (127,128). Increased eye diameter and axial length was highly correlated to the magnitude and cumulative degree of IOP elevation.…”

The Impact of Choroidal Swelling on Optic Nerve Head Deformation

“…From glaucoma studies, we hypothesize that a sustained deformation due to elevation of IOP can stimulate mechanically sensitive cells in the ONH, thereby initiating a biological cascade that results in permanent pathological remodeling. [37][38][39] The impact of persistent choroidal swelling on the surrounding tissues in the ONH thus merits further investigation, particularly since the choroid is a dynamic tissue that is responsive to multiple stimuli, including pharmacological and positional challenges among others. [40][41][42][43][44] Importantly, our findings illustrate the strong importance of choroidal anatomy on ONH biomechanics.…”

Potential mechanisms of retinal ganglion cell type‐specific vulnerability in glaucoma

“…5 It is characterised by an unobstructed irido-corneal drainage angle and a gradual remodelling of the connective tissue support at the optic nerve head. 6 Glaucoma can be associated with, but not defined by age-related IOP elevation, caused by increased resistance to aqueous outflow through the trabecular meshwork. 4 In the absence of IOP elevation it is classified as normal-tension glaucoma.…”