A novel recombinant human microplasminogen induced complete posterior vitreous detachment without morphological change of retina in juvenile rabbits

Exp Eye Res. 2023 May:230:109465. doi: 10.1016/j.exer.2023.109465. Epub 2023 Apr 6.

Abstract

Vitreomacular traction syndrome results from persistent vitreoretinal adhesions in the setting of partial posterior vitreous detachment (PVD). Vitrectomy and reattachment of retina is an effective therapeutic approach. The adhesion between vitreous cortex and internal limiting membrane (ILM) of the retina is stronger in youth, which brings difficulties to induce PVD in vitrectomy. Several clinical investigations demonstrated that intravitreous injection of plasmin before vitrectomy could reduce the risk of detachment. In our study, a novel recombinant human microplasminogen (rhμPlg) was expressed by Pichia pastoris. Molecular docking showed that the binding of rhμPlg with tissue plasminogen activator (t-PA) was similar to plasminogen, suggesting rh μPlg could be activated by t-PA to generate microplasmin (μPlm). Moreover, rhμPlg had higher catalytic activity than plasminogen in amidolytic assays. Complete PVD was found at vitreous posterior pole of 125 μg rhμPlg-treated eyes without morphological change of retina in juvenile rabbits via intraocular injection. Our results demonstrate that rhμPlg has a potential value in the treatment of vitreoretinopathy.

Keywords: Microplasmin; Posterior vitreous detachment; Recombinant human microplasminogen; Retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Humans
  • Injections, Intraocular
  • Molecular Docking Simulation
  • Plasminogen / metabolism
  • Plasminogen / pharmacology
  • Rabbits
  • Retina
  • Retinal Diseases* / metabolism
  • Serine Proteases
  • Tissue Plasminogen Activator / metabolism
  • Tissue Plasminogen Activator / pharmacology
  • Vitrectomy / methods
  • Vitreous Body / metabolism
  • Vitreous Detachment* / drug therapy

Substances

  • Tissue Plasminogen Activator
  • Plasminogen
  • Serine Proteases