Intravitreal human complement factor H in a rat model of laser-induced choroidal neovascularisation

Br J Ophthalmol. 2013 Mar;97(3):367-70. doi: 10.1136/bjophthalmol-2012-302307. Epub 2012 Dec 19.

Abstract

Purpose: To investigate the inhibitory effect of intravitreally administered human complement factor H (CFH) in a rat model of laser-induced choroidal neovascularisation (CNV).

Methods: Analysis of alternative pathway inhibition by human plasma-purified CFH was conducted by measuring C3 deposition on zymosan particles using rat serum. CNV was induced by laser photocoagulation on Day 0 in the eyes of Brown Norway rats. Human plasma-purified CFH (50 μg/2 μl) or phosphate buffered saline was injected intravitreally on Day 0 (prevention arm) or Day 7 (treatment arm). Seven days after injection, eyes were enucleated and retinal pigment epithelium-choroid-sclera flat mounts were prepared. Areas of CNV were determined in flat mounts and quantified using an image analysis programme. Flat mounts were also stained for membrane attack complex.

Results: In rat serum, human CFH inhibited activity of alternative pathway in a dose-dependent manner. On Day 3, mean membrane attack complex deposition in laser-treated retina significantly decreased in CFH-treated eyes (p<0.001). In the prevention arm, the mean CNV area in CFH-treated eyes decreased by 27.0% compared with phosphate buffered saline-treated control eyes on Day 7 (p=0.011). In the treatment arm, the mean CNV area in CFH-treated eyes decreased by 38.3% compared with control eyes on Day 14 (p=0.001).

Conclusions: Intravitreal injection of human CFH resulted in the suppression of formation of new, and regression of preformed laser-induced CNV in the rat model. Human CFH may be a feasible treatment for CNV associated with age-related macular degeneration or other causes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Choroidal Neovascularization / drug therapy*
  • Choroidal Neovascularization / etiology
  • Choroidal Neovascularization / pathology
  • Complement Factor H / administration & dosage*
  • Complement Inactivating Agents / administration & dosage
  • Disease Models, Animal
  • Humans
  • Intravitreal Injections
  • Lasers / adverse effects*
  • Rats
  • Rats, Inbred BN
  • Treatment Outcome

Substances

  • Complement Inactivating Agents
  • Complement Factor H