Retinal pigment epithelial debridement as a model for the pathogenesis and treatment of macular degeneration

Am J Ophthalmol. 1996 Nov;122(5):629-43. doi: 10.1016/s0002-9394(14)70481-7.

Abstract

Purpose: To determine the effects of the absence of the retinal pigment epithelium on the choriocapillaris and outer retina by performing retinal pigment epithelial cell debridement with mitomycin C to inhibit cell proliferation pharmacologically in the porcine eye.

Methods: A pars plana vitrectomy was performed in 12 eyes, and two neurosensory retinal detachments per eye were created by injecting 10(-3) mg/ml mitomycin C and 0.25% edetic acid into the subretinal space. Twenty minutes later, the retinal pigment epithelium was debrided, and the retina was reattached with a fluid-gas exchange.

Results: Bruch's membrane was devoid of native retinal pigment epithelium, and the choriocapillaris was patent immediately after debridement. No proliferation of the retinal pigment epithelium occurred 1 week after debridement, and choriocapillaris atrophy was present beneath areas of Bruch's membrane that were devoid of retinal pigment epithelium. Four weeks postsurgery, choriocapillaris atrophy persisted in all debrided blebs, although unpigmented retinal pigment epithelium repopulated portions of Bruch's membrane in one of three blebs. Outer retinal atrophy was present in areas of Bruch's membrane with no retinal pigment epithelium and no choriocapillaris 4 weeks postsurgery. The choriocapillaris was patent in areas of mitomycin C injection without debridement.

Conclusion: Absence of the retinal pigment epithelium leads to atrophy of the choriocapillaris within 1 week after surgery. This finding provides an animal model to study transplantation of retinal pigment epithelium onto bare patches of Bruch's membrane in age-related macular degeneration and other diseases and provides insight into the pathogenesis of nonexudative age-related macular degeneration.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Atrophy
  • Bruch Membrane / pathology
  • Capillaries / pathology
  • Cell Division / drug effects
  • Choroid / blood supply
  • Choroid / pathology
  • Debridement / methods*
  • Disease Models, Animal
  • Female
  • Fluorescein Angiography
  • Fundus Oculi
  • Macular Degeneration / etiology*
  • Macular Degeneration / surgery*
  • Male
  • Mitomycin / pharmacology
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Pigment Epithelium of Eye / pathology
  • Pigment Epithelium of Eye / surgery*
  • Retina / pathology
  • Retinal Detachment / surgery
  • Swine
  • Vitrectomy

Substances

  • Nucleic Acid Synthesis Inhibitors
  • Mitomycin