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    Women's Health

    (M-494) Effects of menopause on ocular tissue stiffness

    Thursday, October 12, 2023
    9:30 AM – 10:30 AM PDT
    Location: Exhibit Hall - Row M - Poster # 494

      Presenting Author(s)

    • NF

      Nina Sara Fraticelli-Guzman, MS

      Graduate Research Assistant
      Georgia Institute of Technology
      Atlanta, Georgia, United States

      • Last Author(s)

    • AF

      Andrew J. Feola

      Assistant Professor
      Emory University & Georgia Institute of Technology, United States

      • Co-Author(s)

    • CE

      C Ross Ethier

      Professor
      Georgia Institute of Technology
      Atlanta, Georgia, United States

    • TS

      Todd Sulchek (he/him/his)

      Professor
      Georgia Institute of Technology, United States

    • AR

      A. Thomas Read

      Research Scientist
      Georgia Institute of Technology & Emory University, United States

    Introduction::

    Glaucoma is the leading cause of irreversible blindness worldwide and affects more women than men. Recent studies have suggested that early menopause and deficiencies in estrogen signaling increase the risk of glaucoma development. However, menopause is not currently considered a risk factor in the clinical management of this disease. A prominent biomechanical event associated with glaucoma is alteration in the stiffness of the key ocular tissue, the trabecular meshwork (TM). While menopause affects the biomechanical properties of tissues throughout the body, it is still unknown how it impacts the mechanical properties of various ocular tissues. Thus, the objective of this work was to study how surgical menopause, via ovariectomy (OVX), impacted the stiffness of ocular tissues.



    Materials and Methods:: Young (3-4 months) female Brown Norway rats were divided into pre- (Naïve; n = 6-8) and post-menopausal (OVX; n = 5-7) cohorts. Eight weeks post-surgery, animals were sacrificed and eyes were enucleated for atomic force microscopy (AFM) measurement of tissue stiffness. For one eye per animal, 2-4 cryosections (10 µm thick) of the eye’s anterior segment were cut and placed on a glass slide. For each cryosection, stiffnesses of the TM, cornea, and sclera were measured using an MFP-3D AFM (Asylum Research, Santa Barbara, CA) and a silicon nitride cantilever with a 5 µm radius borosilicate glass particle as the spherical tip (Novascan Technologies, Inc., Ames, IA). To measure TM stiffness, 15 µm x 15 µm force maps (16 points) were taken at three distinct locations. Within the same cryosection, we also measured the stiffness of the cornea and sclera from a 20 µm x 20 µm force map (36 points total) within each tissue region. Force-displacement curves were fit to the Hertz model to calculate the Young’s modulus (RStudio 4.1.0, Posit Team, Boston, MA). For each force map, the Young’s moduli were pooled, log-transformed, and fit to a normal distribution to obtain a single stiffness value for each tissue region per eye. A Mann-Whitney Test was used to test for statistical differences between cohorts per tissue. For inter-cohort statistical tissue differences, we used a Kruskal-Wallis and reported adjusted p-values from a Mann-Whitney multiple comparisons test using a Bonferroni correction.

    Results, Conclusions, and Discussions::

    Results


    We saw no statistically significant difference in stiffness between the Naïve and OVX cohorts for the TM (p = 0.46), cornea (p= 0.16), or sclera (p = 0.20). However, we observed a consistent pattern of inter-tissue stiffness differences independent of the cohorts. In the Naïve cohort, the sclera was 486% and 368% stiffer vs. the cornea (p = 0.0005) and TM (p = 0.002), respectively. In the OVX cohort, the sclera was 481% and 448% stiffer vs. the cornea (p = 0. 003) and TM (p = 0.012), respectively. For both cohorts, the stiffest tissue was the sclera followed by the TM and the cornea.


    Conclusion


    To better understand the biomechanical effects of menopause, we will expand on this study by increasing our sample size and including middle-aged (9-10 months) and older (20 months) cohorts. Finally, given the TM is known to show segmental flow, we will identify and study the biomechanical properties of these different flow regions in menopause.


    Discussion


    We anticipated finding significant differences in tissue stiffnesses between Naïve and OVX animals as past work has shown that menopause affects the stiffness of other tissues; however, we did not. This may be due to the mode and scale of testing since AFM testing does not entirely capture the physiological loading the eye experiences in vivo. Alternatively, there might not be an observable mechanical difference in the tissues until glaucoma is present. Yet, we did see tissue stiffness differences between cohorts, strongly motivating future studies. Furthermore, we found significant differences in stiffnesses between tissue regions per cohort, and we hypothesize these differences may help keep the eye stable under different conditions.


    Past work has shown the TM is segmented into high and low flow regions, with differences in stiffness between them seen in human glaucomatous eyes, which we did not test. Thus, future work will study the stiffnesses in these flow regions in each cohort. Additionally, since both age and age of menopause may play a role in developing glaucoma, we will expand the ages tested to study how these parameters interact to affect ocular tissue stiffness.



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