Pronerve growth factor induces angiogenesis via activation of trka: Possible role in proliferative diabetic retinopathy

Sally L. Elshaer, Mohammed A. Abdelsaid, Ahmad Al-Azayzih, Parag Kumar, Suraporn Matragoon, Julian J. Nussbaum, Azza B. El-Remessy

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Proliferative diabetic retinopathy (PDR) is the leading cause of blindness in working age Americans. We demonstrated that diabetes disturbs the homeostasis of nerve growth factor (NGF) resulting in accumulation of its precursor proNGF. Increases in proNGF were positively correlated with progression of diabetic retinopathy, having the highest level in ocular fluids from PDR patients compared to nondiabetic patients. Here, we attempted to evaluate the contribution and the possible mechanism of proNGF to PDR. The angiogenic response of aqueous humor samples from PDR patients was examined in human retinal endothelial cells in the presence or absence of anti-proNGF antibody. Additional cultures were treated with mutant-proNGF in the presence of specific pharmacological inhibitors of TrkA and p75 NTR receptors. PDR-aqueous humor samples exerted significant angiogenic response including cell proliferation, migration, and alignment into tube-like structures. These effects were significantly reduced by anti-proNGF antibody but not by IgG. Treatment of retinal endothelial cells with mutant-proNGF activated phosphorylation of TrkA and p38MAPK; however, it did not alter p75 NTR expression. Inhibition of TrkA but not p75 NTR significantly reduced mutant-proNGF-induced cell proliferation, cell migration, and tube formation. Taken together, these results provide evidence that proNGF can contribute to PDR at least in part via activation of TrkA.

Original languageEnglish (US)
Article number432659
JournalJournal of Diabetes Research
Volume2013
DOIs
StatePublished - Sep 23 2013

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Diabetic Retinopathy
Intercellular Signaling Peptides and Proteins
Aqueous Humor
Cell Movement
Anti-Idiotypic Antibodies
Endothelial Cells
Cell Proliferation
Nerve Growth Factor
Blindness
Homeostasis
Immunoglobulin G
Phosphorylation
Pharmacology

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Pronerve growth factor induces angiogenesis via activation of trka : Possible role in proliferative diabetic retinopathy. / Elshaer, Sally L.; Abdelsaid, Mohammed A.; Al-Azayzih, Ahmad; Kumar, Parag; Matragoon, Suraporn; Nussbaum, Julian J.; El-Remessy, Azza B.

In: Journal of Diabetes Research, Vol. 2013, 432659, 23.09.2013.

Research output: Contribution to journalArticle

Elshaer, Sally L. ; Abdelsaid, Mohammed A. ; Al-Azayzih, Ahmad ; Kumar, Parag ; Matragoon, Suraporn ; Nussbaum, Julian J. ; El-Remessy, Azza B. / Pronerve growth factor induces angiogenesis via activation of trka : Possible role in proliferative diabetic retinopathy. In: Journal of Diabetes Research. 2013 ; Vol. 2013.
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