# In vivo Ultrastructure of Chorioretinal Disease

> **NIH NIH R01** · DOHENY EYE INSTITUTE · 2022 · $342,101

## Abstract

Project Summary
This renewal will address crucial knowledge gaps in the pathway that subretinal drusenoid deposits (SDD) lead to
Type 3 macular neovascularization (T3MNV, also known as retinal angiomatous proliferation) in age-related macular
degeneration (AMD). SDD are extracellular lesions present between photoreceptors and their supportive retinal
pigment epithelium (RPE) cells. Thus they’re on the opposite side of the physiologic blood-retina-barrier to classical
drusen, which are AMD’s hallmark lesions. Drusen accumulate on the inner surface of Bruch’s membrane posterior
to the RPE. T3MNV is an important by less recognized form of neovascular AMD that has an intraretinal origin and
can result in severe vision loss. SDD have a strikingly high occurrence in eyes with T3MNV. The distribution of
T3MNV has a large overlap with that of SDD. T3MNV’s etiology is recently appreciated by advanced retinal imaging
including optical coherence tomography (OCT) structure and angiography (OCTA). It’s been suggested that T3MNV
originates from the deep capillary plexus (DCP) of the retina after precursory RPE cells migrate anteriorly. How SDD
lead to T3MNV, and how retinal capillaries interact with precursor migratory RPE cells to initiate T3MNV is not
completely understood. Nor is why and when RPE cells begin migration. We hypothesize that reduced or impaired
metabolic supply due to dysfunction of the choriocapillaris or accumulation of extracellular lesions on both sides of
the RPE are inciting events that promote RPE cells to leave their monolayer and migrate to the DCP, thereby
eliciting neovascularization in the retina; this process can be significantly exacerbated by SDD. We thus propose to
evaluate the health status of the retinal capillary system through in vivo characterization of the retinal capillary
hemodynamics in relation to the developmental stage of SDD and drusen, the health of the RPE, and the structure
of the choriocapillaris and the choroid, in patients with AMD. We’ve developed an adaptive optics (AO) enhanced
high speed near confocal ophthalmoscope (AONCO), which can image the retina with cellular resolution and
measure the high-order hemodynamics in retinal capillaries. We've developed novel method to estimate the
choriocapillaris structure using OCTA. We obtained fluorescence lifetime imaging ophthalmoscopy (FLIO), which
can assess RPE health. Our objectives are two-fold: understanding the pathway by which SDD lead to T3MNV and
developing AO imaging based biomarkers for early detection of T3MNV. We predict: 1. High-order hemodynamic
characteristics that measure the acceleration (and its change) of the blood flow within retinal capillaries may provide
sensitive detection of abnormalities of the retinal microcirculation induced by early neovascular events that lead to
T3MNV. 2. FLIO may provide an objective quantification of RPE health that correlates with the stages of SDD and
drusen, and the health of the choriocapillaris. Success of t...

## Key facts

- **NIH application ID:** 10491689
- **Project number:** 5R01EY024378-08
- **Recipient organization:** DOHENY EYE INSTITUTE
- **Principal Investigator:** Yuhua Liang Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $342,101
- **Award type:** 5
- **Project period:** 2015-01-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491689

## Citation

> US National Institutes of Health, RePORTER application 10491689, In vivo Ultrastructure of Chorioretinal Disease (5R01EY024378-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10491689. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*