# Somatostatin blockade of CNS autonomic hyperactivity for treatment of diabetic retinopathy

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $461,792

## Abstract

We have shown that loss of somatostatin (SST) expression in the hypothalamus is
associated with chronic excitatory activation of brainstem sympathetic autonomic effector
neurons in diabetes. We have evidence that periventricular hypothalamic SST neurons (i.e.
those that innervate brainstem sympathetics) directly innervate bone marrow (BM) and that
preservation of this small, but important population appears to be particularly relevant to prevent
sympathetic hyperactivity. Sympathetic hyperactivity leads to BM dysfunction with an increase in
the generation and release of proinflammatory monocytes that contribute to the development of
diabetic retinopathy (DR). Systemic monocytosis resulting from BM dysfunction also serves to
promote neuroinflammation of the hypothalamus and of brainstem sympathetic autonomic
effector neurons resulting in an auto-perpetuating cycle of excitation of autonomic neurons.
 The central hypothesis emerging from these studies is that restoring SST levels and
neuronal activity in the diabetic hypothalamus to nondiabetic levels will reduce chronic
excitatory activation of brainstem sympathetic autonomic effector neurons, avoid
development of BM pathology and the subsequent systemic and retinal inflammation
leading to DR.
 In Aim 1, we will determine whether loss of SST neuronal activity results in persistent
hypothalamic hyper excitation of brainstem autonomic effector nuclei and chronic over activation
of the BM leading to BM pathology. In Aim 2, we will determine whether restoration of SST
levels using vector expressing SST in hypothalamic neurons of diabetic rodents will reduce
chronic over activation of sympathetic neuronal activity to the BM, prevent/reverse BM
dysfunction and prevent/treat DR. In Aim 3, we will test whether long-term pharmacological
supplementation using intranasal delivery of the somatostatin analogue, octreotide, would
prevent diabetes-induced BM dysfunction and DR, and block hypothalamic inflammation to stop
the auto-perpetuating cycle of excitation of autonomic neurons. SST analogues have been
tested extensively in humans and this strategy could be immediately translated to clinical use by
adopting intranasal administration of SST analogues to reduce diabetes-induced sympathetic
hyperactivity responsible for BM pathology, systemic inflammation and DR.

## Key facts

- **NIH application ID:** 9955265
- **Project number:** 5R01EY028037-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Michael Edwin Boulton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $461,792
- **Award type:** 5
- **Project period:** 2017-09-30 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9955265

## Citation

> US National Institutes of Health, RePORTER application 9955265, Somatostatin blockade of CNS autonomic hyperactivity for treatment of diabetic retinopathy (5R01EY028037-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9955265. Licensed CC0.

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