In vivo measurement of trabecular meshwork stiffness in a corticosteroid-induced ocular hypertensive mouse model

Abstract

SignificanceGlaucoma is the leading cause of irreversible blindness worldwide. The primary and only modifiable risk factor for the development of glaucoma is elevated intraocular pressure (IOP), and lowering IOP effectively slows glaucomatous disease progression. Unfortunately, the majority of available treatments do not target, or intentionally bypass, the diseased and stiffened glaucomatous outflow tissues responsible for IOP elevation. We recently established that conventional outflow tissue stiffness reflects tissue function. Therefore, detection of outflow tissue stiffness using noncontact, noninvasive optical coherence tomography, as we here demonstrate in an animal model of glaucoma, represents a valuable tool for assessing outflow tissue functional status. Such technology has the potential to monitor recently approved treatments targeting the outflow tissues, and to inform glaucoma surgery decisions.

In Vivo Imaging of Schlemm's Canal and Limbal Vascular Network in Mouse Using Visible-Light OCT

“…Figure 4n shows an average reduction of 72% at +10 mm Hg and 26% reduction at +5 mm Hg. As reported by Li et al, 25 the SC size reduces roughly 80% at 20 mm Hg and 37% at 15 mm Hg. Li et al 25 did not set the IOP levels relative to baseline IOP but rather at absolute values.…”

“…As reported by Li et al, 25 the SC size reduces roughly 80% at 20 mm Hg and 37% at 15 mm Hg. Li et al 25 did not set the IOP levels relative to baseline IOP but rather at absolute values. Regardless, the values obtained are comparable to the degree of collapse that we observed.…”

“…50 Although several publications have used OCTA to image the SC in mouse, only B-scan images were shown and the angiography information was used as a tool in segmenting the SC rather than enabling direct visualization of SC. [24][25][26] Although not in its natural physiologic state, the entire structure of SC can be noninvasively and fully reconstructed. Therefore, the enlargement of SC and its uniformity under external perturbation imaged by OCT may be a potential measure to predict the success of certain antiglaucoma surgeries such as laser trabeculoplasty and canaloplasty.…”

“…17,18 Researchers have used OCT to investigate properties of SC in vivo in mice and humans. 17,[19][20][21][22][23][24][25][26] These studies were limited in axial resolution (2-5 μm) and field of view (0.5-3 mm). Imaging the detailed structure of SC in mice requires overcoming several hurdles.…”

Ripasudil in a model of pigmentary glaucoma

“…Several studies found that Rho-kinase inhibitors Y-27632, Y-39983, HA-1077, and H-1152, could increase outflow and decrease IOP by altering the TM cytoskeleton [8,[18][19][20][21] . Stress fibers can contract [22] and increase stiffness [23,24] leading to decreased outflow in primary open-angle glaucoma [25] and also in glucocorticoid-induced glaucoma [26] . In our study, pigment dispersion caused a marked increase in stress fibers and IOP but then dropped to baseline after K-115 treatment.…”