# Mechanisms of neurodegeneration in diabetic retinopathy: Role of spermine oxidase

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2020 · $362,143

## Abstract

PROJECT SUMMARY
Diabetic Retinopathy (DR), a major complication of diabetes, is the leading cause of blindness in working-aged
adults in the United States. DR is characterized by neurodegeneration and microvascular abnormalities. Current
therapies for DR treat advanced stages of the disease, particularly the vasculopathy and have adverse side
effects. Lack of effective treatments to prevent the incidence or progression of DR is a major problem in the
vision field. A critical barrier to the progress in reducing vision loss in diabetic patients is the lack of
understanding of the molecular mechanisms that lead to diabetes-induced neuronal damage which could serve
therapeutic targets. Our goal is to contribute to the treatment of DR, by defining the specific role of Spermine
Oxidase (SMO, an important enzyme in polyamine metabolic pathway), in mediating neuronal damage in the
diabetic retina and by demonstrating its potential as a therapeutic target for DR treatment. Our central
hypothesis is that diabetes causes upregulation of SMO in retinal neurons, resulting in increased polyamine
oxidation and release of acrolein. Our hypothesis predicts that formation of various protein-acrolein adducts
causes oxidative damage in diabetic retina, leading to neuronal dysfunction. Our objectives are: 1) determine
the impact of SMO overexpression/downregulation in mediating neuronal damage and dysfunction in
experimental model of DR; 2) characterize molecular mechanisms involved in SMO-induced neuronal damage
in the diabetic retina, and 3) determine the therapeutic potential of inhibiting SMO in DR. Our expected
outcomes include 1) demonstration of alterations in inner retinal neuronal survival and function in response to
manipulation of SMO expression in DR models; 2) identification of SMO induced molecular changes by which
neuronal damage occurs in diabetic retina; and 3) preservation of retinal structure and function in response to
SMO inhibition in experimental DR model. Our studies will impact the field of diabetic retinopathy by providing
new and significant information on mechanisms by which neurons become dysfunctional in the diabetic retina
and thus can lead to the development of accurate and efficacious targeted therapies to delay or prevent vision
loss in DR patients. The concept of limiting neuronal injury is also applicable to other vision disorders such as
glaucoma and optic neuropathy. Modulating SMO function to reduce oxidative modifications of proteins and
mitochondrial dysfunction in the retina can facilitate towards clinical practice by providing new therapies for vision
loss worldwide. Aim 1 will test the hypothesis that upregulation of SMO causes neuronal injury in the diabetic
retina. Aim 2 will test the hypothesis that upregulation of SMO causes increased polyamine oxidation, acrolein-
protein adducts formation, and mitochondrial dysfunction in the diabetic retina. Aim 3 will test the hypothesis
that SMO blockade can preserve retinal struct...

## Key facts

- **NIH application ID:** 9968271
- **Project number:** 5R01EY028569-03
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Priya Narayanan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $362,143
- **Award type:** 5
- **Project period:** 2018-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968271

## Citation

> US National Institutes of Health, RePORTER application 9968271, Mechanisms of neurodegeneration in diabetic retinopathy: Role of spermine oxidase (5R01EY028569-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9968271. Licensed CC0.

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