Repair in the rabbit outflow system

An in vivo study was conducted to study repair processes in the injured rabbit outflow system. A uniform injury was produced by raising intraocular pressure (IOP) manometrically to 70 mmHg for 1 h. The recovery process, which was followed clinically for 8 weeks and morphologically for 6 weeks, led to the re-establishment of normal meshwork architecture within this period. The morphological studies included light microscopy, autoradiography and electron microscopy. The initial lesion consisted of large deficits in the meshwork with breakdown of cell-to-cell connections, loss of extracellular materials and disruption of the vessels of the aqueous plexus. There was a significant lowering of IOP in the first week of recovery, which thereafter climbed back to normal. Also in the first week the meshwork became infiltrated with inflammatory cells which cleared by 4 weeks. There was some meshwork cell death by either necrosis or apoptosis. The majority of meshwork cells became activated within the first few days and remained activated for at least the first 2 weeks. Tritiated proline incorporation was maximal between 1 and 2 weeks. Tritiated thymidine labelling was seen throughout, but only after the inflammation subsided was it clear that meshwork cells in all regions of the meshwork were proliferating. Our study provided no evidence that normal meshwork cells have a basal proliferative turnover level. Our injury model involved complete repair of the outflow tissues and that required meshwork cells to become activated, mobilise, undertake synthetic activity and proliferate. This is the first example, other than argon laser trabeculoplasty, where meshwork cells in vivo have been induced to divide. Possible therapeutic implications for glaucoma are discussed.