Cellular-Scale Imaging in the Living Eye to Study Glaucoma Pathophysiology

To construct and test a new advanced multifunctional imaging system capable of revealing astounding details as small as single cells in the living eye and transforming the future of clinical testing.

Aim 1: Construct a multifunctional AO-OCT/SLO instrument designed for imaging the non-human primate at the cellular scale with targeted probes and experimental manipulations. Aim 2: Establish ranges of parameter variability for key quantitative measures of anatomical, physiological, biomechanical, and intrinsic optical properties of retinal cells and tissues. Aim 3: Validate in vivo observations by histopathology. We will use immunohistochemistry and microscopy to evaluate postmortem tissue samples corresponding to the same areas imaged by AO-OCT/SLO in Aim 2.

We will construct a new instrument designed for the non-human primate to study glaucoma pathophysiology. The instrument enables quantitative three-dimensional morphometry, elastography, polarimetry, reflectometry, angiography, optoretinography, and fluorescence imaging, all at the cellular scale in the living eye, by introducing a new polarization-sensitive interferometer and fluorescence channel. Our image registration software enables simultaneous detection of OCT and fluorescence signals without requiring additional hardware, easing longitudinal assessment of proposed biomarkers.

We anticipate that our results using this dedicated laboratory system will lead directly to meaningful insights and impactful advances in our knowledge about glaucoma pathophysiology and treatment efficacy that

1. directly impact the interpretation of current clinical standard imaging modalities,
2. inform sample size requirements for subsequent studies designed to test therapeutic interventions, and
3. extend the limits of what events and relationships can be detected in the living eye, particularly in the context of identifying reversible stages of glaucoma pathophysiology.