Purpose
To study biochemical and cellular changes in primary open angle glaucomatous (POAG) sclera. TGF-β is a soluble protein known to be elevated in POAG and implicated in trabecular meshwork (TM) pathologic changes leading to increased aqueous humor outflow resistance and elevated intraocular pressure. As the TM is not entirely occluded in POAG, this soluble factor can still travel beyond the TM into the distal outflow pathway, including the intrascleral venous plexus, where it can mediate pathologic alterations such as myofibroblastic differentiation and elevated α-smooth muscle actin expression.
Methods
Scleral samples have been collected from an age-matched pair of 60 year-old glaucomatous and non-glaucomatous patients. Glaucomatous sclera was collected during canaloplasty surgery from a female with a five-year history of glaucoma with visual field defects and elevated intraocular pressures (20-40 mm Hg) despite multiple aqueous suppressants and a prostaglandin. Control sclera was collected from remnant corneo-scleral rim after corneal transplantation. Scleral samples were homogenized and myofibroblastic activation was evaluated by assessing α-smooth muscle actin expression. GAPDH levels served as protein loading controls.
Results
Expression of α-smooth muscle actin expression was greater in glaucomatous sclera than in age-matched non-glaucomatous sclera.
Conclusions
Elevated α-smooth muscle actin levels in glaucomatous sclera are consistent with TGF-β mediated alterations and scleral myofibroblastic induction. These results support further evaluation of TGF-β mediated scleral changes and the relevance of myofibroblastic activation in glaucoma. Additional scleral samples from glaucomatous and control patients will be collected and evaluated. Primary culture fibroblasts will also be generated from normal and glaucomatous sclera and compared.
Keywords: 708 sclera •
519 extracellular matrix •
568 intraocular pressure