# Novel Therapeutic Strategies for Retinal Vascular Inflammation and Angiogenesis in Diabetic Retinopathy.

> **NIH NIH K08** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $196,646

## Abstract

PROJECT SUMMARY/ABSTRACT
 As a pediatric ophthalmologist concerned by the growing incidence of obesity, metabolic syndrome,
and diabetes in the pediatric population, especially in Hispanic patients, I have chosen to focus my research on
diabetic retinopathy. Inflammation and angiogenesis herald the development of vision-threatening
complications of diabetic retinopathy (DR), including retinal edema, hemorrhages, glaucoma and detachments.
Vascular endothelial growth factor (VEGF) inhibitors are the standard of care drugs used to treat vision
threatening DR complications; however, their effectiveness is limited to certain patient populations and no
alternative therapies have emerged into clinical practice. The chemokine CXCL8, which is known to affect
pathologic mechanisms associated with DR, accumulates in the eyes of diabetics and its levels correlate with
DR progression. However, we do not fully understand the functional implications of its induction and
subsequent accumulation. We have found that multiple pro-inflammatory and pro-angiogenic molecules
associated with DR induce CXCL8 in human retinal cells, and that CXCL8 can affect human retinal endothelial
cell responses associated with DR onset and progression. I believe that CXCL8 is a key intermediary at the
juncture of multiple signaling pathways that regulate and promote both early and late events in DR pathology,
including VEGF signaling. Therefore, CXCL8 receptors may be ideal targets for novel DR therapies. Several
inhibitors of CXCL8 receptors are in clinical trials for non-ocular conditions, yet their potential to interfere with
mechanisms of DR in the retina has not been explored. I believe that there is value in testing these inhibitors in
clinical trials and repurposing them to treat patients with DR. However, before pursuing that goal, the
significance of CXCL8 induction in the eye in relation to mechanisms of DR pathology (Aim 1) and the value of
these inhibitors to interfere with those mechanisms (Aim 2) must be rigorously evaluated. I intend to do this
using a stepwise approach complimenting human primary cell culture-based in vitro assays (Müller glia and
vascular endothelial cells, Aim1), with in vivo mouse models of DR-associated pathologic events
(Streptozotocin-induced diabetes and oxygen-induced retinopathy models, Aim 2). Confirming the ability of
commercially-available CXCL8 receptor inhibitors to block DR-relevant pathogenic processes would affirm their
therapeutic potential to treat DR, and inform the design of future pre-clinical and clinical trials. This mentored
experience will allow me to generate pilot data to successfully compete for R-level funding, to advance the
understanding of DR pathophysiology, and to accelerate the development of new DR therapies, therefore
promoting my independence as a clinician investigator. The skills, collaborative relationships, and data
acquired by the execution of this proposal and its training plan, along with my ophthalmology t...

## Key facts

- **NIH application ID:** 9954087
- **Project number:** 5K08EY029006-03
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Dolly Ann Padovani-Claudio
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,646
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954087

## Citation

> US National Institutes of Health, RePORTER application 9954087, Novel Therapeutic Strategies for Retinal Vascular Inflammation and Angiogenesis in Diabetic Retinopathy. (5K08EY029006-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9954087. Licensed CC0.

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