July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Trabecular meshwork stiffness and outflow resistance are related
Author Affiliations & Notes
  • C Ross Ethier
    Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
  • Ke Wang
    Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
  • Guorong Li
    Duke University Eye Center, Durham, North Carolina, United States
  • A Thomas Read
    Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
  • Iris Navarro
    Duke University Eye Center, Durham, North Carolina, United States
  • Ashim K Mitra
    School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri, United States
  • W Daniel Stamer
    Duke University Eye Center, Durham, North Carolina, United States
  • Todd Sulchek
    Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   C Ethier, None; Ke Wang, None; Guorong Li, None; A Read, None; Iris Navarro, None; Ashim Mitra, None; W Daniel Stamer, None; Todd Sulchek, None
  • Footnotes
    Support  Georgia Research Alliance (CRE) and the BrightFocus Foundation (GL)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3970. doi:
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      C Ross Ethier, Ke Wang, Guorong Li, A Thomas Read, Iris Navarro, Ashim K Mitra, W Daniel Stamer, Todd Sulchek; Trabecular meshwork stiffness and outflow resistance are related. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3970.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Trabecular meshwork (TM) stiffness is elevated in glaucoma patients vs. unaffected individuals (Last, IOVS, 2011; Wang et al., 2017). However, glaucoma eyes in these studies were treated with glaucoma medications, a possible confounding factor. Here we explore whether there is a relationship between TM stiffness and conventional outflow resistance in 2 strains of wild-type mice and in a steroid mouse glaucoma model.

Methods : In all mice, outflow facility (C) was measured by ocular perfusion and TM stiffness (E) was measured by atomic force microscopy on thawed cryosections (Wang et al., EER, 2016). In Study 1, we used untreated wild-type C57BL/6J (n=18) and CBA/J (n=10) mice. In Study 2, we used custom nano-sized polymers loaded with either dexamethasone (DEX; n=25 mice) or vehicle (n=16), injected into the subconjunctival/periocular space of C57BL/6J mice. IOP was measured twice per week (TonoLab).

Results : In Study 1, C was slightly lower in CBA/J vs. C57BL/6J (Mean±SD: 6.17 ± 2.91 vs. 6.28 ± 2.18 mmHg/nl/min) while the TM was stiffer in CBA/J (3.08 ± 3.55 kPa) than in C57BL/6J (2.20 ± 1.12 kPa); however, neither difference was statistically significant. In Study 2, IOP of DEX mice was elevated vs. control mice on the day of sacrifice (27.1 ± 2.7 vs. 20.5 ± 3.2mmHg; P<0.001). C of DEX mice was lower than for control mice (3.05 ± 1.47 vs. 4.09 ± 1.71mmHg; P=0.192). The TM in DEX mice was stiffer than that in control mice, but this difference was not statistically significant (2.38 ± 1.31 vs. 1.99 ± 0.91 kPa; P=0.357). Importantly, TM stiffness significantly correlated with outflow resistance (1/C) within each study (Study 1: R2=0.35, P=0.006; Study 2: R2=0.41, P=0.002; Figure 1).

Conclusions : TM stiffness is positively correlated with conventional outflow resistance in two wild-type mouse strains and after DEX treatment in C57BL/6J mice. This is consistent with human data and suggests that TM stiffness is intimately involved in establishing outflow resistance. This finding motivates development of techniques to measure TM stiffness in vivo, as a surrogate for TM function, and development of novel therapeutic approaches based on reducing TM stiffness to lower IOP.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Outflow resistance (1/C) vs. TM stiffness for DEX (n=11) and control mice (n=10). The blue line and equation represent the linear regression of the pooled data, with 95% confidence bounds for the regression in grey. Different shapes represent different mouse cohorts.

Outflow resistance (1/C) vs. TM stiffness for DEX (n=11) and control mice (n=10). The blue line and equation represent the linear regression of the pooled data, with 95% confidence bounds for the regression in grey. Different shapes represent different mouse cohorts.

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