Abstract
Purpose: :
To determine the effect of cochlin expression in the trabecular meshwork (TM) on intraocular pressure (IOP) in DBA/2J-Gpnmb+/SjJ, DBA/2J and DBA/2J cochlin knockout mice.
Methods: :
DBA/2J-Gpnmb+/SjJ (at 3 to 8 months of age; n=42-48 for each vector at each age) and DBA/2J cochlin knockout (at 6 months of age; n=20) mice were intracamerally injected with a lentiviral vector bearing the COCH-GFP transgene, GFP alone or human serum albumin (HSA). DBA/2J mice (3 to 8 months old; n=38-45 at each age) were injected with a vector bearing cochlin shRNA or a non-mammalian control shRNA in the anterior chamber. IOP measurements were carried out using the Tonolab or intraocular cannulation. Eyes were enucleated and optic nerve damage was assessed using paraphenylenediamine (PPD) staining of eye tissues. All studies were performed adhering to the ARVO Statement for the Use of Animals in Research.
Results: :
DBA/2J-Gpnmb+/SjJ mice injected with COCH-GFP demonstrated a rise in IOP concomitant with cochlin expression, in contrast to control mice injected with GFP alone or HSA. DBA/2J mice injected with cochlin shRNA showed a decrease in IOP compared to controls. Re-introduction of COCH into the anterior chamber of DBA/2J cochlin knockout mice results in elevated IOP. Increased expression of cochlin was commensurate with IOP elevation. The optic nerve damage correlated with elevated IOP.
Conclusions: :
The level of cochlin expression in the TM influences the level of IOP. This present work suggests cochlin is involved in the regulation of intraocular pressure.
Keywords: extracellular matrix • intraocular pressure • trabecular meshwork