# The role of plasmacytoid dendritic cells in ocular angiogenesis

> **NIH NIH R01** · TUFTS MEDICAL CENTER · 2020 · $495,599

## Abstract

Project Summary
Angiogenesis is precisely regulated by a balance of growth factors, chemokines, proteases, and inflammatory
cells. Macrophages, monocytes, and conventional dendritic cells (cDCs) are involved in all stages of
angiogenesis from degradation of local extracellular matrix to proliferation of endothelial cells and capillary
formation. Despite the well-studied functions of these cells in angiogenesis, the role and source of endogenous
anti-angiogenic molecules which preserve corneal angiogenic privilege or prevent retinal neovascularization is
elusive. Moreover, the impact of recently identified plasmacytoid dendritic cells (pDCs), a vital subset of
immune cells that reside in the cornea and retina, remains to be determined. These cells orchestrate and link
innate and adaptive immune responses and are implicated in the induction of tolerance to transplanted tissues
or tumors. Our preliminary experiments showed that depletion of pDCs is accompanied by abrupt and severe
breakdown of angiogenic privilege of cornea and corneal pDCs co-stain with Endostatin, a well-known anti-
angiogenic molecule. We hypothesize that pDCs exhibit anti-angiogenic functions by actively secreting anti-
angiogenic molecules and are necessary for preserving corneal angiogenic privilege as well as limiting retinal
neovascularization in pathologic conditions. Our aims include identification of pro- and anti-angiogenic
molecules expressed by pDCs and their functional relevance on corneal angiogenic privilege, characterizing
the impact of pDCs on the avascular state of the cornea in steady-state and during inflammation, describing
the molecular and cellular participants involved in pDC-mediated inhibition of corneal angiogenesis during
neovascularization, and assessing how activation of pDCs through activation of toll like receptors (TLR)-7 and
TLR-9 via their synthetic agonists as well as Herpes Simplex Virus, their natural activator, affects
angiogenesis. Further, we aim to assess the impact of pDCs in preventing oxygen- as well as laser-induced
choroidal neovascularization and study the effectiveness of adoptive transfer of pDCs for treatment of retinal
neovascularization in these conditions. The application proposes a paradigm shift in our understanding of the
regulation of angiogenesis and corneal vascular privilege. Our fresh perspective on how pDCs contribute to
avascular state of cornea and restrict retinal neovascularization has applications beyond ocular tissues. It
would potentially introduce new therapeutic avenues in various pathologic conditions in which attenuation of
angiogenesis would be potentially beneficial such as cancers and inflammatory diseases, as well as in
conditions which induction of angiogenesis is advantageous, particularly in ischemic conditions.

## Key facts

- **NIH application ID:** 9893891
- **Project number:** 5R01EY026963-04
- **Recipient organization:** TUFTS MEDICAL CENTER
- **Principal Investigator:** Pedram Hamrah
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $495,599
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893891

## Citation

> US National Institutes of Health, RePORTER application 9893891, The role of plasmacytoid dendritic cells in ocular angiogenesis (5R01EY026963-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9893891. Licensed CC0.

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