# Vascular Gene Delivery and Early Disease Biomarkers in Diabetic Retinopathy

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2021 · $360,868

## Abstract

ABSTRACT c
The vasculature endothelium forms a selectively permeable barrier that facilitates transfer of nutrients,
oxygen and waste products between the retina and the blood. Therefore, diseases affecting the structure
and function of the vascular endothelium, such as diabetic retinopathy (DR) and age-related macular
degeneration (AMD), have a devastating effect on the health of the retina and ultimately lead to severe
visual impairment. Traditional treatment approaches focus on ameliorating disease symptoms that lead to
vision loss, including retinal and choroidal neovascularization. Whilst effective, treatments such as laser
photocoagulation are both invasive and destructive, requiring frequent interventions throughout the patient's
lifetime, leading to the ablation of neurosensory retina as new blood vessels are cauterized. Moreover,
these treatments fail to address the pathologic abnormalities within vascular endothelial cells (VECs) that
underlie abnormal blood vessel function in DR. As such, they serve only to temporarily limit progression of
the disease. In contrast to existing treatments, gene therapy represents an attractive therapeutic alternative,
potentially allowing for the permanent correction of vascular dysfunction prior to the development of sight-
threatening complications. The inability to efficiently deliver genetic material to vascular endothelial
cells currently prohibits development of any gene therapy treatment aimed at preventing DR. We
have recently taken the first step to overcoming this barrier by elucidating a recombinant adeno-associated
virus (rAAV) vector mutant with enhanced affinity for VECs. We propose to further develop these vector
technologies and optimize their surgical delivery through the following specific aims: 1) Evaluate endothelial
cell transduction and maintenance of gene expression in normal and diabetic vasculature; 2) Characterize
early stage biomarkers of DR progression and efficacy of endothelial cell gene therapy, and 3) Assess
endothelial cell transduction following rAAV administration by selective intra-ophthalmic artery infusion
(SIOAI). Utilizing a well-established rat model of type I diabetes (T1D) we anticipate the development of a
strategy to effectively deliver genetic material in both normal and dysfunctional VECs. In doing so, we will
utilize various advanced imaging modalities to quantin order to maximize the clinical translation of the
proposed DR gene therapy, we will optimize key aspects relating to the targeted intravascular delivery of
rAAV using a mini-swine model that accurately recapitulates human cardiovascular and ocular anatomy.
The Ocular Gene Therapy Laboratory (OGTL) and Advanced Ocular Imaging Program (AOIP) at the
Medical College of Wisconsin, together the University of Florida Department of Ophthalmology, provide the
perfect collaborative environment to complete the proposed work. Finally, our proposal addresses an
emerging need identified in the NEI Publication “V...

## Key facts

- **NIH application ID:** 10247765
- **Project number:** 5R01EY027767-04
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Daniel Mark Lipinski
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $360,868
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247765

## Citation

> US National Institutes of Health, RePORTER application 10247765, Vascular Gene Delivery and Early Disease Biomarkers in Diabetic Retinopathy (5R01EY027767-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10247765. Licensed CC0.

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