Anti-secretogranin III therapy of oxygen-induced retinopathy with optimal safety

Fen Tang, Michelle E. LeBlanc, Weiwen Wang, Dan Liang, Ping Chen, Tsung Han Chou, Hong Tian, Wei Li

Research output: Contribution to journalArticle

Abstract

Retinopathy of prematurity (ROP) with pathological retinal neovascularization is the most common cause of blindness in children. ROP is currently treated with laser therapy or cryotherapy, both of which may adversely affect the peripheral vision with limited efficacy. Owing to the susceptibility of the developing retina and vasculatures to pharmacological intervention, there is currently no approved drug therapy for ROP in preterm infants. Secretogranin III (Scg3) was recently discovered as a highly disease-restricted angiogenic factor, and a Scg3-neutralizing monoclonal antibody (mAb) was reported with high efficacy to alleviate oxygen-induced retinopathy (OIR) in mice, a surrogate model of ROP. Herein we independently investigated the efficacy of anti-Scg3 mAb in OIR mice and characterized its safety in neonatal mice. We developed a new Scg3-neutralizing mAb recognizing a distinct epitope and independently established the therapeutic activity of anti-Scg3 therapy to alleviate OIR-induced pathological retinal neovascularization in mice. Importantly, anti-Scg3 mAb showed no detectable adverse effects on electroretinography and developing retinal vasculature. Furthermore, systemic anti-Scg3 mAb induced no renal tubular injury or abnormality in kidney vessel development and body weight gain of neonatal mice. In contrast, anti-vascular endothelial growth factor drug aflibercept showed significant side effects in neonatal mice. These results suggest that anti-Scg3 mAb may have the safety and efficacy profiles required for ROP therapy.

Original languageEnglish (US)
JournalAngiogenesis
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Retinopathy of Prematurity
Monoclonal Antibodies
Oxygen
Safety
Pathologic Neovascularization
Retinal Neovascularization
Neutralizing Antibodies
Cryotherapy
Therapeutics
Electroretinography
Kidney
Drug therapy
Angiogenesis Inducing Agents
Laser Therapy
Blindness
Premature Infants
Vascular Endothelial Growth Factor A
Weight Gain
Retina
secretogranin III

Keywords

  • Angiogenic factor
  • Anti-angiogenic therapy
  • Oxygen-induced retinopathy
  • Retinopathy of prematurity
  • Scg3
  • Secretogranin III

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cancer Research

Cite this

Anti-secretogranin III therapy of oxygen-induced retinopathy with optimal safety. / Tang, Fen; LeBlanc, Michelle E.; Wang, Weiwen; Liang, Dan; Chen, Ping; Chou, Tsung Han; Tian, Hong; Li, Wei.

In: Angiogenesis, 01.01.2019.

Research output: Contribution to journalArticle

Tang, Fen ; LeBlanc, Michelle E. ; Wang, Weiwen ; Liang, Dan ; Chen, Ping ; Chou, Tsung Han ; Tian, Hong ; Li, Wei. / Anti-secretogranin III therapy of oxygen-induced retinopathy with optimal safety. In: Angiogenesis. 2019.
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