The impact of age-related vitreous degeneration and vitreous replacement on scleral biomechanics: a novel mechanism and treatment target for glaucoma

Abstract
Background: Glaucoma is a leading cause of blindness worldwide. While the potential
mechanisms of glaucomatous injury are incompletely understood, it is clear that the incidence of
glaucoma increases with age and with intraocular pressure (IOP). Several biomechanical studies
have indicated that the sclera is a critical mediator of the biomechanical response of the optic
nerve head (ONH) to changes in IOP, showing a significant progressive stiffening with aging in
the regions around the ONH (peripapillary sclera) most susceptible to glaucomatous injury. While
prior studies have provided valuable insight into the role of IOP, cerebrospinal fluid pressure,
blood pressure, and structural stiffness of the ONH and lamina cribrosa , as determinants of the
ONH‘s mechanical environment, the role of the vitreous humor, filling the space between ONH-
retina and lens, has still not been investigated as being part of the ONH’s environment.
Significantly, the vitreous undergoes progressive structural degeneration with aging showing
increasing liquid and decreasing gel volumes throughout life that impairs its viscoelastic
properties. We therefore propose that such an age-related vitreous degeneration along scleral
stiffening is determinant to ONH biomechanics. The Objectives of this study are: 1) to determine
the impact of vitreous in modulating the biomechanical scleral response during dynamic IOP
variations in human donor eyes; 2) To determine how scleral response can be biomechanically
improved with a biomimetic designed hydrogel. Design: In a group of 20 human donor eyes over
age of 40, we will measure the sclera’s response during physiological IOP variations induced in
the anterior chamber. We will compare the scleral biomechanics in four conditions of the vitreous
chamber: i) with the natural vitreous, ii) after replacing the liquid part of the vitreous with saline,
iii) after replacing the remaining vitreous gel with saline, iv) and after replacement with a
biomimetic hydrogel designed to match the viscoelastic properties of young vitreous. Impact:
Elucidating the complex mechanical relationship between the sclera and vitreous will not only
inform and improve mechanistic models of glaucoma, it will also provide a potential translational
mechanism to develop novel approaches to attenuate the mechanical insult caused by dynamic
IOP variations on the ONH. This project will be the first to define this relationship, filling a scientific
gap. Vitreous replacement based on the ONH-sclera response can be further explored in clinical
longitudinal studies and animal models based on the data obtained herein.
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Grant Number: 5R21EY035035-02
NIH Institute/Center: NIH
Principal Investigator: Gianfranco Bianco