# Correction of diabetic retinopathy by mitochondrial transfer

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2024 · $538,307

## Abstract

Mitochondria play cornerstone role in cellular metabolism and mitochondrial
fragmentation, swelling and loss of cristae, epigenetic changes in mitochondrial DNA, reduction
of transport proteins, and mitochondria-ER regulation precede histopathological abnormalities in
DR. Recent studies demonstrate that mitochondrial transfer can rescue cells from bioenergetic
abnormalities and cell death [1-8]. We propose that normalization of retinal endothelial cell
bioenergetics by mitochondrial transfer can prevent retinal vascular degeneration and provide a
novel breakthrough approach to treatment of DR. Accumulating evidence suggests that retinal
vascular degeneration occurs when diabetic metabolic insult causes both retinal damage and
defective repair by bone marrow-derived circulating vascular reparative cells, called CD34+ cells
based on the critical surface marker that identifies them for isolation. In healthy subjects, CD34+
cells participate in the retinal vascular repair process by migrating and homing to the site of
endothelial injury, while this capability is lost in CD34+ cells from diabetic subjects with vascular
complications. Previously, we demonstrated that bone marrow pathology with CD34+ cell
dysfunction precedes and is necessary for retinal vascular degeneration in diabetes. CD34+ cells
repair by paracrine mechanism and was recently shown to include mitochondrial transfer
nanotunnels or through extracellular vesicles-mediated mechanism. Release of mitochondrial
DNA and proteins by damaged retinal endothelial cells stimulate mitochondrial biogenesis in
stem/progenitor cells followed by the transfer of mitochondria to the injured resident cells.
Alterations that impair the ability of diabetic CD34+ cells to repair injured vascular cells are not
completely understood and will be studied in this application. is one of the questions addressed
in this application. We hypothesize that retinal endothelial cells (REC) mitochondria are damaged
and mitochondria are not repaired because of deficiency in i) initiation of mitochondrial transfer
by CD34+ cells, ii) quality of CD34+cell mitochondria, and iii) the CD34+ cells sensing of resident
endothelial cell mtDNA/proteins released during injury. To test hypothesis, the following Specific
Aims will be addressed: Aim 1: To determine the signals and mechanisms that initiate repair of
damaged retinal endothelial cells by mitochondrial transfer. Aim 2: To examine the mitochondrial
transfer by CD34+ cells from diabetic and nondiabetic donors in db/db mice.

## Key facts

- **NIH application ID:** 10873892
- **Project number:** 5R01EY034133-02
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Maria Bartolomeo Grant
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $538,307
- **Award type:** 5
- **Project period:** 2023-07-01 → 2024-05-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873892

## Citation

> US National Institutes of Health, RePORTER application 10873892, Correction of diabetic retinopathy by mitochondrial transfer (5R01EY034133-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10873892. Licensed CC0.

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