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.

Segmental outflow and trabecular meshwork stiffness in an ocular hypertensive mouse model

“…vs. CON: 0.673 ± 0.330 a.u.) consistent with previous reports of DEX-induced α-SMA upregulation 41,42 . However, no significant differences were detected with linear mixed-effects modeling between LF and HF regions within either group, or in the interaction between DEX-treatment and flow region (Figure 9C).…”

Segmental outflow and trabecular meshwork stiffness in an ocular hypertensive mouse model

“…vs. CON: 0.673 ± 0.330 a.u.) consistent with previous reports of DEX-induced α-SMA upregulation 41,42 . However, no significant differences were detected with linear mixed-effects modeling between LF and HF regions within either group, or in the interaction between DEX-treatment and flow region (Figure 9C).…”

Anti-fibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis

“…We deduced TM tissue stiffness values of 22 kPa in the NT-treated group vs. 61 kPa in the PL-treated group ( Figure 3G ). The latter value is consistent with the TM stiffness we previously measured in DEX-NP treated eyes of 69 kPa ( Li et al, 2019 ). Notably, the TM stiffness we estimated in NT-treated eyes was close to the value of 29 kPa that we previously determined in naïve eyes ( Li et al, 2019 ; Figure 3—figure supplement 2 ).…”

“…The latter value is consistent with the TM stiffness we previously measured in DEX-NP treated eyes of 69 kPa ( Li et al, 2019 ). Notably, the TM stiffness we estimated in NT-treated eyes was close to the value of 29 kPa that we previously determined in naïve eyes ( Li et al, 2019 ; Figure 3—figure supplement 2 ). Thus, it appears that NT returns TM stiffness to near control levels after only 4 days of administration in eyes made hypertensive by long-term GC administration.…”

A Histomorphometric and Computational Investigation of the Stabilizing Role of Pectinate Ligaments in the Aqueous Outflow Pathway

“…For example, by comparing modeled SCLA vs. experimentally observed SCLA changes with IOP, a significant stiffening of TM was observed with age (Li et al, 2023). Of note, our predicted TM stiffness for young mice (∼29 kPa (Li et al, 2023)) was consistent with previous results on young mice (Li et al, 2019). We also predicted that elderly eyes had the smallest Ultimate nSCLA for a given TM/PL stiffness (Figure 6A).…”

Segmental outflow and trabecular meshwork stiffness in an ocular hypertensive mouse model

“…vs. CON: 0.673 ± 0.330 a.u.) consistent with previous reports of DEX-induced α-SMA upregulation 41,42 . However, no significant differences were detected with linear mixed-effects modeling between LF and HF regions within either group, or in the interaction between DEX-treatment and flow region (Figure 9C).…”

Anti-fibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis

“…We deduced TM tissue stiffness values of 22 kPa in the NT-treated group vs. 61 kPa in the PL-treated group ( Figure 3G ). The latter value is consistent with the TM stiffness we previously measured in DEX-NP treated eyes of 69 kPa ( Li et al, 2019 ). Notably, the TM stiffness we estimated in NT-treated eyes was close to the value of 29 kPa that we previously determined in naïve eyes ( Li et al, 2019 ; Figure 3—figure supplement 2 ).…”

“…The latter value is consistent with the TM stiffness we previously measured in DEX-NP treated eyes of 69 kPa ( Li et al, 2019 ). Notably, the TM stiffness we estimated in NT-treated eyes was close to the value of 29 kPa that we previously determined in naïve eyes ( Li et al, 2019 ; Figure 3—figure supplement 2 ). Thus, it appears that NT returns TM stiffness to near control levels after only 4 days of administration in eyes made hypertensive by long-term GC administration.…”

A Histomorphometric and Computational Investigation of the Stabilizing Role of Pectinate Ligaments in the Aqueous Outflow Pathway

“…For example, by comparing modeled SCLA vs. experimentally observed SCLA changes with IOP, a significant stiffening of TM was observed with age (Li et al, 2023). Of note, our predicted TM stiffness for young mice (∼29 kPa (Li et al, 2023)) was consistent with previous results on young mice (Li et al, 2019). We also predicted that elderly eyes had the smallest Ultimate nSCLA for a given TM/PL stiffness (Figure 6A).…”

Segmental outflow and trabecular meshwork stiffness in an ocular hypertensive mouse model

“…vs. CON: 0.673 ± 0.330 a.u.) consistent with previous reports of DEX-induced α-SMA upregulation 41,42 . However, no significant differences were detected with linear mixed-effects modeling between LF and HF regions within either group, or in the interaction between DEX-treatment and flow region (Figure 9C).…”

Anti-fibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis

“…We deduced TM tissue stiffness values of 22 kPa in the NT-treated group vs. 61 kPa in the PL-treated group ( Figure 3G ). The latter value is consistent with the TM stiffness we previously measured in DEX-NP treated eyes of 69 kPa ( Li et al, 2019 ). Notably, the TM stiffness we estimated in NT-treated eyes was close to the value of 29 kPa that we previously determined in naïve eyes ( Li et al, 2019 ; Figure 3—figure supplement 2 ).…”

“…The latter value is consistent with the TM stiffness we previously measured in DEX-NP treated eyes of 69 kPa ( Li et al, 2019 ). Notably, the TM stiffness we estimated in NT-treated eyes was close to the value of 29 kPa that we previously determined in naïve eyes ( Li et al, 2019 ; Figure 3—figure supplement 2 ). Thus, it appears that NT returns TM stiffness to near control levels after only 4 days of administration in eyes made hypertensive by long-term GC administration.…”

A Histomorphometric and Computational Investigation of the Stabilizing Role of Pectinate Ligaments in the Aqueous Outflow Pathway

“…For example, by comparing modeled SCLA vs. experimentally observed SCLA changes with IOP, a significant stiffening of TM was observed with age (Li et al, 2023). Of note, our predicted TM stiffness for young mice (∼29 kPa (Li et al, 2023)) was consistent with previous results on young mice (Li et al, 2019). We also predicted that elderly eyes had the smallest Ultimate nSCLA for a given TM/PL stiffness (Figure 6A).…”