Induction of myopia leads to a decreased glycosaminoglycan synthesis and smaller collagen fibrillar diameters, increased levels of gelatinase-A (MMP-2) and decreased amounts of tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in the fibrous sclera of both chicks and tree shrews. Another factor found to be involved in altered eye growth is the transforming growth factor beta-2 (TGFbeta-2). The aim of the current study was to measure MMP-2, TIMP-2 and TGFbeta-2 mRNA expression changes separately in the two scleral layers of chicks, following myopic and hyperopic defocus. Chicks were treated unilaterally with positive and negative lenses for different time periods. All contralateral eyes wore plano lenses and additional controls, treated binocularly with plano lenses, were included. Real-time PCR was used to measure MMP-2, TIMP-2 and TGFbeta-2 mRNA levels. Few changes in MMP-2 and TIMP-2 mRNA levels were measured following treatment with plus and minus lenses for up to 3 days. The mRNA levels of MMP-2 and TIMP-2 were either unchanged or co-regulated in both eyes, even though only the eye with the powered lens actually displayed changes in growth. In contrast, TGFbeta-2 mRNA was significantly up-regulated in the cartilaginous layer following treatment with plus lenses after 24 hr, compared to all other groups. These changes were confined to the eyes that also displayed reduced growth, suggesting a role of TGFbeta-2 in the final steps of visual eye growth regulation.