# VRC: A Stem Cell-Based Treatment Strategy for Laser-Induced Permanent Retinal Damages

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $236,900

## Abstract

Eye damage can be caused by various sources in a battlefield. Laser devices widely used by the armed forces
can lead to irreversible loss of photoreceptors (PRs) and damage to the choroid, leading to permanent visual
loss. Currently there are no effective treatments for laser-induced permanent retinal damage. Cell replacement
therapy is a major hope for structural and functional reconstruction of a retina permanently damaged by laser.
The proposed study's objective is to develop a cellular therapy for laser eye injuries by using a “total retina patch”
made of healthy RPE, an artificial Bruch's membrane (BM), and sheets of retina organoids (RO). Our hypothesis
is that permanent retinal damage can be repaired (and vision improved) by using this stem-cell-derived tissue-
engineered co-graft. A combination graft made of RO sheets and polarized RPE sheets cultured over an artificial
BM will produce a structural reconstruction of a severely damaged retina, and lost vision will be more improved
using a co-graft than a transplant of either RPE alone or retina organoid alone. Since the RPE monolayer is
integral to maintaining healthy PRs, and interacts with the PRs in the phototransduction cycle, we think that the
presence of a healthy polarized RPE monolayer and structural support from intact and healthy BM will provide a
beneficial microenvironment for regenerating the RO sheets. Further, the parylene membrane can protect the
co-graft from the pathological BM surface of the diseased host eye to prevent BM abnormalities from unfavorably
altering the transplanted cells' behavior. This hypothesis will be tested in two different laser damage animal
models that represent military-relevant injuries: (1) Rat model for retinal laser damage. (2) Rabbit laser damage
model having eye size more comparable to that of humans. NIH nude rats and Normal Dutch Belted rabbits will
be exposed to laser after anesthesia and pupil dilation. Vision loss will be confirmed by electroretinogram (ERG)
and behavioral testing after laser exposure. The animals will receive co-graft implants or control surgeries. Vision
loss will be confirmed by electroretinogram (ERG). The following experimental groups will be used for the 2 Aims:
(a) Transplants of sheets of human embryonic stem cell (hESC)-RO+RPE+BM; Age-matched Controls include:
(b) RO sheets only; (c) RPE sheets only; (d) no surgery. Immunodeficient rats will be used in all experiments to
avoid graft rejection without the negative effects of immunosuppression drugs. Transplant placement will be
verified by optical coherence tomography (OCT). The rats' vision will be tested monthly by optokinetic/ visual
discrimination testing and ERG. At the end of the experiment (3-6 months post transplantation), visual responses
will be mapped in the superior colliculus by electrophysiology. Investigators will be masked to the rats'
experimental condition. Rabbits will be euthanized 2 months post-surgery. Rat and rabbit retinas will be analyzed...

## Key facts

- **NIH application ID:** 10206151
- **Project number:** 5R01EY031144-03
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Biju Blavady Thomas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $236,900
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10206151

## Citation

> US National Institutes of Health, RePORTER application 10206151, VRC: A Stem Cell-Based Treatment Strategy for Laser-Induced Permanent Retinal Damages (5R01EY031144-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10206151. Licensed CC0.

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