Development and characterization of a new rat ocular hypertension model induced by intracameral injection of conjunctival fibroblasts

Sci Rep. 2019 Apr 29;9(1):6593. doi: 10.1038/s41598-019-43048-2.

Abstract

Glaucoma is a chronic optic neuropathy that leads to visual field loss. Elucidating the mechanisms underlying glaucoma is essential for developing new treatments, such as neuroprotective drugs. Various glaucoma models based on the induction of intraocular pressure (IOP) elevation have been established for use in glaucoma studies. However, the time-dependent pathological changes accompanying IOP elevation have not been fully elucidated. In this study, rat conjunctival fibroblasts were injected into the anterior chamber of rat eyes, and IOP elevation was induced for 28 days. Glaucomatous signs such as optic nerve head cupping, retinal thinning, glial activation and apoptotic signaling in the retina were obvious in the cell-injected eyes on the 14th day after injection. The pattern of retinal ganglion cell (RGC) loss differed by the magnitude of IOP elevation. The number of RGCs decreased by 37.5% in eyes with IOP lower than 50 mmHg (Under-50) and by 88.0% in those with IOP higher than 50 mmHg (Over-50) 28 days after cell injection. The RGC counts were correlated with IOP in the Under-50 group but not in the Over-50 group. Our model may contribute to the investigation of pathogenic mechanisms of glaucoma and the development of new glaucoma treatments.

MeSH terms

  • Animals
  • Conjunctiva / pathology
  • Conjunctiva / transplantation*
  • Disease Models, Animal
  • Fibroblasts / pathology
  • Fibroblasts / transplantation*
  • Glaucoma / drug therapy
  • Glaucoma / pathology*
  • Humans
  • Injections
  • Intraocular Pressure / drug effects
  • Neuroprotective Agents
  • Ocular Hypertension / drug therapy
  • Ocular Hypertension / etiology
  • Ocular Hypertension / pathology*
  • Optic Disk / pathology
  • Rats
  • Retina / metabolism
  • Retina / pathology
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / pathology
  • Tonometry, Ocular

Substances

  • Neuroprotective Agents