# Mitochondrial factories for AMD therapy

> **NIH EY R56** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2026 · $1,029,472

## Abstract

PROJECT SUMMARY
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness involving gradual
dysfunction and degeneration of photoreceptors and the retinal pigment epithelium (RPE). Mitochondrial
dysfunction represents a hallmark of AMD. Excessive and persistent reactive oxygen species (ROS) damages
mitochondrial DNA (mtDNA), resulting in fewer mitochondria. Impairments in respiratory chain activity and
reduced oxidative phosphorylation (OXPHOS) impacts ATP synthesis and further drives ROS production. Our
prior work has shown that exogenous mitochondrial transplantation to cells can induce a bioenergetic shift
towards increased OXPHOS and ATP production, and reduced ROS. Mitochondrial cell-to-cell transfer in
response to stress rescues aerobic respiration to reduce deleterious cell dynamics. We aim to create a
sustainable source of mitochondria proximal to the RPE in the form of mesenchymal stem cells (MSCs)
transfected with nuclear respiratory factor 1 (NRF1), a driver of mitochondrial biogenesis, for enhanced cell-to-
cell transfer of mitochondria. Our objectives are to determine how NRF1 transfection changes MSC
transcriptional activity, mitochondrial production and trafficking, and extracellular vesicle (EV) contents, and test
the strategy in two rodent models of retinal degeneration. We hypothesize that our cell therapy using NRF1-
overexpressing MSCs will not only provide the needed energetic boost via mitochondrial mass transfer to retinal
cells, but also induce profound cellular reprogramming through the secretion of EV-containing factors, thereby
counteracting and potentially reversing the onset of late-stage dry AMD. We will use a combination of molecular
and biochemical methods, including transcriptomics, to characterize the potency of mitochondrial transfer to
impact AMD. We will first investigate the impact of NRF1 on mitochondrial transfer mechanisms in MSCs. We
will elucidate the role of NRF1 on mitochondrial transfer mechan

## Key facts

- **NIH application ID:** 11494029
- **Project number:** 1R56EY036406-01A1
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** ELVIN  BLANCO
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** EY
- **Fiscal year:** 2026
- **Award amount:** $1,029,472
- **Award type:** 1
- **Project period:** 2026-05-01T00:00:00 → 2028-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11494029

## Citation

> US National Institutes of Health, RePORTER application 11494029, Mitochondrial factories for AMD therapy (1R56EY036406-01A1). Retrieved via AI Analytics 2026-07-02 from https://api.ai-analytics.org/grant/nih/11494029. Licensed CC0.

---

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