Abstract
Purpose:
Glaucoma filtering surgery failure is frequently associated with excessive subconjunctival fibrosis, which may occur as consequence of fibroblast activation. Losartan potassium (LP), an angiotensin-1 receptor inhibitor, has been studied as a new healing modulator. Thus we evaluated the effects of losartan on proliferation of rabbits’ Tenon’s capsule fibroblasts (RTF).
Methods:
Fibroblasts obtained from New Zealand rabbits were cultured in Dulbecco's modified Eagle's medium (DMEM). The dose dependent effects of LP (i.e. 0.3, 1.0 and 3.0 μM) on third passage cell proliferation were determined in triplicate after 24 h or 48 h with the MTT assay. Immunofluorescence of alpha smooth muscle actin (alpha-SMA) assessed myofibroblast differentiation. Real-time reverse transcription polymerase chain reaction evaluated type I alpha I collagen (COL1A1) gene expression.
Results:
LP (3.0 μM) after 24 h or 48 h inhibited RTF proliferation compared to its controls by 51% and 40%, respectively (p<0.001 ; p=0,0004). Moreover, decreased myofibroblast transdifferentiation by at least 25% was observed. All LP concentrations also suppressed COL1A1 mRNA expression levels, after 48 h (p=0.002).
Conclusions:
Suppression by LP of RTF proliferation, as well as myofibroblast transdifferentiation and COL1A1 gene expression suggests that LP may decrease in vivo fibrosis. Such a result indicates LP could be used as adjunctive treatment, improving the outcome of glaucoma filtration surgery.
Keywords: 654 proliferation