# hiPSC-derived tissue mimetics of the retina blood barrier

> **NIH NIH R21** · UNIVERSITY OF ROCHESTER · 2020 · $192,500

## Abstract

The retinal pigment epithelium (RPE)-Bruch’s Membrane (BrM)-choriocapillaris (CC) complex is a highly
selective diffusional barrier for nutrients and metabolic wastes in the eye. Dysfunctions in the RPE-BrM-CC
complex underlies eye pathologies such as age-related macular degeneration (AMD), the leading cause of
adult blindness in the US. Within the RPE-BrM-CC, BrM is a multilayered tissue that divides RPE and CC and
is the first structure to show anomalies in AMD, yet it is not clear whether RPE and/or CC dysfunction initiates
BrM alterations. Murine models fail to recapitulate AMD since mice lack macula. The inability to use animal
models or recreate a functional RPE-BrM-CC tissue complex limits our ability to investigate crucial aspects of
eye diseases, including AMD, where the integrity of the entire tissue is compromised. Therefore, we
hypothesize that by using developmentally-inspired cues, a functional tissue mimetic can be developed for ex
vivo study. Specifically, we will exploit human induced pluripotent stem cell (hiPSC) technology and tissue
engineering to establish functional tissue mimetics. Because of their modularity, hiPSC-derived in vitro models
allow the flexibility to study the role individual cell type(s) and intercellular interaction in disease
pathophysiology. Our strong preliminary data demonstrate that hiPSC-RPE seeded onto RGDS-functionalized
poly(ethylene glycol) (PEG) hydrogels are stable and become pigmented over 2-3 weeks. RPE layers deposit
basement membrane, composed of some BrM components. Furthermore, CC-like vasculature, complete with
Col6-postiive basement membrane, can be developed from hiPSC-endothelial cells (EC) and mesenchymal
stem cells (MSC) entrapped within the PEG hydrogels underlying RPE. However, our current tissue mimetic
lacks structurally complete BrM, which limits overall tissue mimetic structure and function. During development,
RPE cells differentiate and become pigmented with support from underlying mesenchymal matrix and soluble
cues. Then the CC layer develops while the mature BrM is deposited by coordinated interplay of the RPE and
CC. Thus, to improve the mimetic, our aims are to 1) exploit developmentally-inspired cues to further enhance
BrM structural development. In Aim 1a, the temporal introduction of the CC tissue mimetics after hydrogel-
seeded RPE layer maturation/pigmentation and in Aim 1b, soluble mesenchymal cues via co-culture, will be
explored to further promote BrM development. Aim 2 will assess the RPE-BrM-CC mimetic function as
compared to in vivo levels and gold standard RPE culture models. Our expertise with engineering biomaterials
to regulate the cell environment (Benoit) and eye physiology and hiPSC-derived RPE, MSC, and EC cell types
is crucial to developing RPE-BrM-CC tissue mimetics using patient-derived cells. Successful completion of
these aims would be a significant step towards ocular disease modeling and subsequent development of novel
drug therapies for several ...

## Key facts

- **NIH application ID:** 9843006
- **Project number:** 1R21EY030817-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Danielle S. Benoit
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,500
- **Award type:** 1
- **Project period:** 2020-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843006

## Citation

> US National Institutes of Health, RePORTER application 9843006, hiPSC-derived tissue mimetics of the retina blood barrier (1R21EY030817-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9843006. Licensed CC0.

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