Purpose: To clarify the role of bone morphogenetic proteins (BMP-2,-4,-5) in sclera remodeling during myopia induction and their effect on sclera fibroblasts in cell culture.
Methods: Reverse transcription and polymerase chain reaction (RT-PCR) as well as immunofluorescence were used to detect the expression of the BMPs in human and guinea pig posterior sclera. In guinea pig form-deprivation myopia (FDM) model, RT-PCR and western blotting were used to investigate changes of BMP expression in the posterior sclera. Human sclera fibroblast (HSF) was primarlly cultured and treated with various doses of BMP-2. Cell proliferation was evaluated by the MTT assay. RT-PCR and western-blot were used to determine the changes of collagen I, aggrecan, and possible activated signal pathway. Cell phenotype and activated signal pathway, especially for α-smooth muscle actin (α-SMA) and phospho-smad1/5/8 were then further investigated by cytoimmunofluorescence staining.
Results: Both human and guinea pig sclera express BMP-2, -4, and -5. In FDM eyes, BMP-2 and BMP-5 expression were reduced in the posterior sclera. Cell proliferation increased significantly (p<0.05) and more cells differentiated into myofibroblast when incubated with 100 ng/ml BMP-2 . The expressions of collangen I, aggrecan, and phospho-smad1/5/8 significantly increased (p<0.05 respectively) as well.
Conclusions: Various BMPs were expressed in human and guinea pig sclera. In the posterior sclera, the expressions of BMP-2 and BMP-5 decreased in FDM eyes. BMP-2 might be able to promote HSF proliferation and differentiation, as well as to help extracellular matrix synthesis potentially through classical Smad pathway.