Tissue Transglutaminase Elevates Intraocular Pressure in Mice

Area of Science:

• Ophthalmology
• Molecular Biology
• Biochemistry

Background:

• Tissue transglutaminase 2 (TGM2) is found at higher levels in glaucomatous trabecular meshwork (TM) tissues.
• Glaucoma is characterized by elevated intraocular pressure (IOP), often linked to increased resistance in aqueous humor outflow through the TM.

Purpose of the Study:

• To investigate if increased TGM2 expression elevates extracellular matrix crosslinking in the TM.
• To determine if this crosslinking increases aqueous humor outflow resistance and consequently elevates IOP in mouse eyes.

Main Methods:

• Cultured human and mouse TM cells were transduced with adenovirus expressing TGM2 (Ad5.TGM2).
• Ad5.TGM2 was injected intravitreally into mouse eyes to measure IOP and aqueous outflow facility.
• Immunohistochemistry was used to assess TGM2 expression and crosslinking in mouse TM.

Main Results:

• Ad5.TGM2 treatment increased N-ε(γ-glutamyl) lysine crosslinks in TM cells and mouse eyes.
• Intravitreal Ad5.TGM2 injection significantly elevated IOP in both BALB/cJ and C57BL/6J mice compared to controls.
• Aqueous outflow facility was significantly reduced in eyes injected with Ad5.TGM2.

Conclusions:

• Increased TGM2 expression in the TM leads to enhanced crosslinking, increased outflow resistance, and elevated IOP in mice.
• TGM2 may be a contributing factor to ocular hypertension in primary open-angle glaucoma (POAG).