# Cross-species vascular anatomy and sensitivity to intraocular pressure in glaucoma

> **NIH NIH R01** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2022 · $497,629

## Abstract

SUMMARY
Vascular dysfunction, with or without elevated intraocular pressure (IOP), is believed to be an important risk
factor in glaucoma and other neuropathies. However, the link between vascular dysfunction and the mechanisms
leading to the characteristic visual field defects in glaucoma is not fully understood. This is partly due to the lack
of a solid quantitative understanding of the 3D architecture of the vasculature of the optic nerve head (ONH), its
anatomical relationship with the load-bearing connective tissues, and how it is affected by IOP. Our overarching
hypothesis is that features of the vasculature and its relationship with the connective tissues predispose
certain ONH regions to compromised perfusion and that this susceptibility is amplified by elevated IOP.
To test this hypothesis, we will sequentially collect in vivo, ex vivo, and histological 3D morphological and
biomechanical data on vascular and connective tissues of the ONH in normal eyes and in eyes with experimental
glaucoma (EG). We will focus on the critical lamina cribrosa (LC) region in three species: human, monkey
(closest model to human, collagenous LC), and mouse (most used model, no collagenous LC). In Aim 1, we will
map in 3D the vasculature and connective tissues of the ONHs of humans, monkeys, and mice, and analyze
these maps quantitatively including by watershed analysis. We predict that zones of visual loss in early glaucoma
will correspond to regions with the most vulnerable vascular supply, e.g., sparse capillaries with low connectivity
and low perfusion redundancy. We postulate that, in primates, not all LC beams have a capillary, and conversely,
that some capillaries are not within a robust collagen-rich beam. We will also address the clinically important
question to which extent in vivo OCT angiography visualizes the smaller or deeper vessels inside the ONH. In
Aim 2, we will perform ex vivo inflation tests on monkey and mouse eyes to quantify the effects of acute IOP
elevation on vessel perfusion and biomechanics, and the LC beams support. Our preliminary data suggests that
“unprotected” vessels may be particularly vulnerable to mechanical distortion, which could, in turn, affect blood
flow. In Aim 3, we will characterize the effects of chronic IOP elevation on vessels and beams. Specifically, we
will compare eyes before and after chronic IOP elevation (EG), and with the contralateral control. This will allow
us to discern characteristics that pre-dispose an eye to glaucoma from those that are the result of the disease.
We will test the hypothesis that the patterns of vessel sensitivity to elevated IOP in mice (that have only a glial
lamina) are different from those in primates. Combining multiple imaging modalities across the same ONHs in
three species will provide cross-verification of the techniques, and deeper insights into the role of LC collagenous
beams supporting the ONH vasculature under normal and elevated IOP. These experiments will help iden...

## Key facts

- **NIH application ID:** 10493356
- **Project number:** 5R01EY031708-02
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Tatjana Claudia Jakobs
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $497,629
- **Award type:** 5
- **Project period:** 2021-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10493356

## Citation

> US National Institutes of Health, RePORTER application 10493356, Cross-species vascular anatomy and sensitivity to intraocular pressure in glaucoma (5R01EY031708-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10493356. Licensed CC0.

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