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

Angiogenesis. 2019 Aug;22(3):369-382. doi: 10.1007/s10456-019-09662-4. Epub 2019 Jan 14.


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.

Keywords: Angiogenic factor; Anti-angiogenic therapy; Oxygen-induced retinopathy; Retinopathy of prematurity; Scg3; Secretogranin III.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Neutralizing / therapeutic use
  • Chromogranins / antagonists & inhibitors*
  • Female
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Intravitreal Injections
  • Kidney / drug effects
  • Kidney / growth & development
  • Kidney / pathology
  • Male
  • Mice, Inbred C57BL
  • Oxygen
  • Retinal Vessels / drug effects
  • Retinal Vessels / pathology
  • Retinal Vessels / physiopathology
  • Retinopathy of Prematurity / drug therapy*
  • Retinopathy of Prematurity / physiopathology
  • Weight Gain / drug effects


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Chromogranins
  • secretogranin III
  • Oxygen