Abstract
Purpose: :
Matrix metalloproteinase-9 (MMP-9) is an extracellular matrix remodeling protease that may play a neuroprotective role in glaucoma. This led to our interest in applying the hypertonic saline injection model of elevated intraocular pressure to investigate the pathophysiology of MMP-9 knockout in mice.
Methods: :
30 MMP-9 KO mice and 30 matched controls were obtained from Jackson Labs and elevated intraocular pressure was induced through injection of hypertonic saline into the episcleral vessels. One eye was injected and the contralateral eye was used as a control. IOP was measured weekly in conscious mice using a TonoLab rebound tonometer. Control and treated eyes were collected under sedation at 350-450mmdays, 550-650mmdays, and greater than 750mmdays. Cross sections of the optic nerves taken approximately 1mm posterior to the optic nerve head were stained with toluidine blue, and axon counts were obtained in a masked fashion for both control and treated eyes using the Zeiss KS400 Image Analysis system. The % axon survival was calculated and tested for significance with the Student’s t-test.
Results: :
Elevated intraocular pressure was successfully induced in all mice and resulted in a loss of axons in both groups. In comparing these two groups, the percent loss in the WT was approximately 20% greater than in the MMP-9 KO.
Keywords: ganglion cells • intraocular pressure • neuroprotection