June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Impact of Neural Crest Derived Foxc2 on the Schlemm’s Canal Examined with visible-light Optical Coherence Tomography
Author Affiliations & Notes
  • Raymond Fang
    Biomedical Engineering, Northwestern University, Evanston, Illinois, United States
  • Pieter Norden
    Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Lisa Beckmann
    Biomedical Engineering, Northwestern University, Evanston, Illinois, United States
  • Tsutomu Kume
    Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Hao Zhang
    Biomedical Engineering, Northwestern University, Evanston, Illinois, United States
  • Footnotes
    Commercial Relationships   Raymond Fang None; Pieter Norden None; Lisa Beckmann None; Tsutomu Kume None; Hao Zhang Opticent Health, Code O (Owner)
  • Footnotes
    Support  NIH grants R01EY028304, 1R01EY029121, R01EY028304, U01EY033001, and T32GM142604.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4402 – F0081. doi:
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      Raymond Fang, Pieter Norden, Lisa Beckmann, Tsutomu Kume, Hao Zhang; Impact of Neural Crest Derived Foxc2 on the Schlemm’s Canal Examined with visible-light Optical Coherence Tomography. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4402 – F0081.

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

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Abstract

Purpose : Glaucoma, a leading cause of blindness, is associated with increased aqueous outflow resistance. Aqueous outflow primarily occurs through the conventional outflow pathway, which includes the trabecular meshwork and Schlemm’s Canal (SC). We investigated the role that neural crest (NC)-derived Foxc2 has on the structural development of SC in vivo.

Methods : Foxc2fl/fl and NC-Foxc2-/- (NC-Foxc2-KO) mice were generated. A TonoLab rebound tonometer measured the intraocular pressure (IOP) of mice under deep anesthesia to establish the baseline IOP level. An anterior segment visible-light optical coherence tomography (vis-OCT) system was used to visualize the SC. Only NC-Foxc2-/- with a mild phenotype, having a visually intact anterior segment under a surgical microscope, were imaged. The anterior chamber was cannulated, and the IOP was adjusted to -10 mmHg, -5 mmHg, 0 mmHg, +5 mmHg, and +10 mmHg relative to the baseline IOP. At each IOP level, the SC volume in a 1.5mm by 1.8mm field of view in the nasal quadrant was measured. Additionally, the average SC height and width were found by fitting an ellipse to the segmented SC for each cross-sectional B-scan image (Fig. 1A-B).

Results : Both Foxc2fl/fl and NC-Foxc2-/- mice had an inverse relationship between IOP and SC volume and height. The SC volume was between 34 and 42% smaller in NC-Foxc2-/- relative to Foxc2fl/fl mice at IOP levels from -10 to +5 mmHg relative to baseline (Fig. 1C). No statistically significant difference in SC volume was found at +10 mmHg. The SC height was between 20 and 23% smaller in NC-Foxc2-/- relative to Foxc2fl/fl mice at IOP levels from -10 to 0 mmHg relative to baseline. The SC width was 17 to 18% smaller in NC-Foxc2-/- relative to Foxc2fl/fl mice at IOP levels of 0 to +5 mmHg relative to baseline.

Conclusions : The decreased SC volume in NC-Foxc2-/- mice relative to Foxc2fl/fl mice suggests that NC-specific deletion of Foxc2 influences the structure of SC and conventional outflow pathway. As SC height is less in NC-Foxc2-/- mice at -10 and -5 mmHg, Foxc2 has a crucial influence on the proper development of the aqueous outflow pathway and trabecular meshwork.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

Fig 1. A,B) Representative B-scans from NC-Foxc2-/- and Foxc2fl/fl mice with SC found within red box. C) Relative SC volumes as a function of IOP and genotype. Statistically significant differences indicated with *.

Fig 1. A,B) Representative B-scans from NC-Foxc2-/- and Foxc2fl/fl mice with SC found within red box. C) Relative SC volumes as a function of IOP and genotype. Statistically significant differences indicated with *.

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