Cochlin Expression in Anterior Segment Organ Culture Models after TGFβ2 Treatment

PURPOSE. To determine the effect of transforming growth factor (TGF)-beta 2 treatment on intraocular pressure (IOP), outflow facility, and cochlin expression in vitro in monkey and pig organ-cultured anterior segments (MOCAS and POCAS). METHODS. MOCAS (rhesus and cynomolgus) or POCAS were infused with media containing 10 ng/mL TGF beta 2 to one segment of each pair and 0.1% BSA (vehicle) to the contralateral segment for up to 14 days at a constant rate. Cochlin expression was determined by immunohistochemical study, ELISA, and Western blot analysis using chicken polyclonal antibodies against different regions of cochlin. RESULTS. TGF beta 2 infusion produced elevated IOP in MOCAS (usually after 5 days), that was approximately 45% greater than baseline and compared to control segments. Outflow facility (OF) was decreased by similar to 40% compared with pretreatment baseline (n = 5). In POCAS (n = 7), IOP was increased (similar to 3 days) by similar to 75% compared with baseline and contralateral changes. The IOP elevation subsided thereafter. Cochlin levels increased with duration of TGF beta 2 treatment in the media and in the region of the trabecular meshwork in both species. CONCLUSIONS. TGF beta 2-induced IOP elevation was associated with an increase in cochlin secretion into the media and expression in the tissue of MOCAS and POCAS. Whether cochlin overexpression contributes to elevated IOP or is a consequence of other changes relevant to IOP elevation remains to be determined. (Invest Ophthalmol Vis Sci. 2009;50:551-559) DOI:10.1167/iovs.08-2632