Reliability of the mouse model of choroidal neovascularization induced by laser photocoagulation

Stephen H Poor1, Yubin Qiu1, Elizabeth S Fassbender1

  • 1Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States.

Abstract

Insights

Reproducing studies on laser-induced choroidal neovascularization (CNV) in mice showed that complement factors C3 and C5, and animal vendor significantly impact CNV, while siRNA and cobra venom factor do not. We offer methods to improve reproducibility.

Area of Science:

  • Ophthalmology
  • Immunology
  • Genetics

Background:

  • Choroidal neovascularization (CNV) is a key pathological feature in several blinding eye diseases.
  • The mouse laser-induced CNV model is widely used to study CNV pathogenesis and test potential therapies.
  • Reproducibility of results in this model can be affected by various experimental factors.

Purpose of the Study:

  • To reproduce published findings on factors influencing laser-induced CNV in mice, including small interfering RNA (siRNA), cobra venom factor, complement factors C3 and C5, and complement receptor C5aR.
  • To investigate the impact of the animal vendor on laser-induced CNV.
  • To provide recommendations for enhancing the reproducibility of the mouse laser-induced CNV model.

Main Methods:

  • Standardized procedures were used to assess reagents and genotypes previously reported to influence CNV.
  • Retrospective analysis of control or placebo mice from multiple experiments was conducted to evaluate vendor effects on CNV area.
  • Specific agents like siRNA, PMX53 (C5a receptor inhibitor), and cobra venom factor were administered to mice undergoing laser photocoagulation.

Main Results:

  • siRNA, PMX53, and cobra venom factor did not substantially impact laser-induced CNV in mice.
  • Mice lacking complement factors C3 or C5 showed altered CNV compared to wild-type controls, with variations depending on the vendor (Jackson Laboratory vs. Taconic).
  • Retrospective analysis revealed that mice from Jackson Laboratory and Charles River exhibited less neovascularization than those from Taconic.

Conclusions:

  • Complement factors C3 and C5, as well as the animal vendor, significantly influence laser-induced CNV in mice.
  • Experimental factors such as siRNA and cobra venom factor did not demonstrate a substantial impact on CNV in this study.
  • Standardized methods and careful consideration of animal source are recommended to improve reproducibility and minimize bias in the mouse laser-induced CNV model.

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