Racioethnic Differences in Human Posterior Scleral and Optic Nerve Stump Deformation.

Purpose: The purpose of this study was to quantify the biomechanical response of human posterior ocular tissues from donors of various racioethnic groups to better understand how differences in these properties may play a role in the racioethnic health disparities known to exist in glaucoma. Methods: Sequential digital image correlation (S-DIC) was used to measure the pressure-induced surface deformations of 23 normal human posterior poles from three racioethnic groups: African descent (AD), European descent (ED), and Hispanic ethnicity (HIS). Regional in-plane principal strains were compared across three zones: the optic nerve stump (ONS), the peripapillary (PP) sclera, and non-PP sclera. Results: The PP scleral tensile strains were found to be lower for ED eyes compared with AD and HIS eyes at 15 mm Hg (P = 0.024 and 0.039, respectively). The mean compressive strains were significantly higher for AD eyes compared with ED eyes at 15 mm Hg (P = 0.018). We also found that the relationship between tensile strain and pressure was significant for those of ED and HIS eyes (P < 0.001 and P = 0.004, respectively), whereas it was not significant for those of AD (P = 0.392). Conclusions: Our results suggest that, assuming glaucomatous nerve loss is caused by mechanical strains in the vicinity of the optic nerve head, the mechanism of increased glaucoma prevalence may be different in those of AD versus HIS. Our ONS strain analysis also suggested that it may be important to account for ONS geometry and material properties in future scleral biomechanical analysis.

2-Photon Characterization of Optical Proteolytic Beacons for Imaging Changes in Matrix-Metalloprotease Activity in a Mouse Model of Aneurysm.

Abdominal aortic aneurysm is a multifactorial disease that is a leading cause of death in developed countries. Matrix-metalloproteases (MMPs) are part of the disease process, however, assessing their role in disease initiation and progression has been difficult and animal models have become essential. Combining Förster resonance energy transfer (FRET) proteolytic beacons activated in the presence of MMPs with 2-photon microscopy allows for a novel method of evaluating MMP activity within the extracellular matrix (ECM). Single and 2-photon spectra for proteolytic beacons were determined in vitro. Ex vivo experiments using the apolipoprotein E knockout angiotensin II-infused mouse model of aneurysm imaged ECM architecture simultaneously with the MMP-activated FRET beacons. 2-photon spectra of the two-color proteolytic beacons showed peaks for the individual fluorophores that enable imaging of MMP activity through proteolytic cleavage. Ex vivo imaging of the beacons within the ECM revealed both microstructure and MMP activity. 2-photon imaging of the beacons in aneurysmal tissue showed an increase in proteolytic cleavage within the ECM (p<0.001), thus indicating an increase in MMP activity. Our data suggest that FRET-based proteolytic beacons show promise in assessing MMP activity within the ECM and will therefore allow future studies to identify the heterogeneous distribution of simultaneous ECM remodeling and protease activity in aneurysmal disease.