Perspectives on biomechanical growth and remodeling mechanisms in glaucoma

Abstract

Glaucoma is a blinding diseases in which damage to the axons results in loss of retinal ganglion cells. Experimental evidence indicates that chronic intraocular pressure elevation initiates axonal insult at the level of the lamina cribrosa. The lamina cribrosa is a porous collagen structure through which the axons pass on their path from the retina to the brain. Recent experimental studies revealed the extensive structural changes of the lamina cribrosa and its surrounding tissues during the development and progression of glaucoma. In this perspective paper we review the experimental evidence for growth and remodeling mechanisms in glaucoma including adaptation of tissue anisotropy, tissue thickening/thinning, tissue elongation/shortening and tissue migration. We discuss the existing predictive computational approaches that try to elucidate the potential biomechanical basis of theses growth and remodeling mechanisms and highlight open questions, challenges, and avenues for further development.

Changes in lamina cribrosa and prelaminar tissue after deep sclerectomy

“…Structural changes of the LC and its surrounding tissues during the development and progression of glaucoma have already been described. 22,23 On the other hand, we did not find significant statistical correlation between structural changes and preoperative prelaminar thickness or RNFL thickness.…”

The Connective Tissue Components of Optic Nerve Head Cupping in Monkey Experimental Glaucoma Part 1: Global Change

“…While each phenomenon is measured individually, our parameter post-BMO total prelaminar volume 7,9 captures all three. Third, connective tissue remodeling 11,12,15 not only contributes to the stiffening processes whereby reversible deformations become permanent, it separately underlies the phenomena of laminar insertion migration, 9,16,17 laminar thickness change, 11 and retrolaminar septal recruitment. 11 The purpose of this report is to identify the principal components of ONH connective tissue deformation and remodeling in monkey experimental glaucoma.…”

A poroelastic model for the perfusion of the lamina cribrosa in the optic nerve head

“…Many clinical and experimental observations suggest that the response of the laminar tissue to changes in IOP is not uniform. For example, loss of collagen fibers was reported in the top-centre of the lamina and recruitment of new collagen was detected at the lower surface, causing cupping in the lamina of animals suffering from prolonged IOP elevation [5]. It would be interesting to further develop the model to investigate whether and to what extent this non-uniform growth and remodeling of the collagen within the lamina is mediated by blood perfusion and availability of nutrients.…”

“…Many studies have indicated that chronical IOP elevation induces significant structural changes in a thin porous tissue at the base of the optic nerve head called lamina cribrosa [2][3][4][5][6]. Elevated IOP may lead to vision loss by inducing mechanical damage on the retinal ganglion cells axons passing through the lamina (mechanical hypothesis) [7,8] and/or by altering the blood flow within the lamina's tissue (hemodynamical hypothesis) [9,10].…”

“…Elevated IOP may lead to vision loss by inducing mechanical damage on the retinal ganglion cells axons passing through the lamina (mechanical hypothesis) [7,8] and/or by altering the blood flow within the lamina's tissue (hemodynamical hypothesis) [9,10]. It is reasonable to expect that the mechanical deformations of a living tissue would affect blood flow within the tissue, and therefore the mechanical and hemodynamical hypotheses should be addressed as one coupled problem [5,11]. In this paper, we develop a mathematical framework that allows, for the first time, to theoretically investigate the coupling between the mechanical and hemodynamical hypotheses concerning the effect of IOP elevation on the lamina's tissue.…”