Statins inhibit TGFβ2 mediated fibrotic response in astrocytes
Reviewed by Graham Wallace

Glaucoma is a common condition where increased ocular pressure can lead to death of retinal ganglion cells due to impaired drainage of fluid from the eye. One mechanism involved in glaucoma is remodelling of the extracellular matrix at the lamina cribrosa (LC) at the optic nerve head, with thinning and displacement causing axonal damage. Transforming growth factor beta2 (TGFβ) defines a family of multifunctional cytokines involved in tissue remodelling and wound healing. TGFβ2 is the predominant form of the family found in the eye, and production by astrocytes is increased in the optic nerve head of patients with glaucoma. Treatment of cultured astrocytes with TGFβ2 led to increased expression of extracellular matrix proteins. Statins are best known for their ability to lower LDL cholesterol in the blood and have been widely prescribed for cardiovascular conditions. Previous work has shown that statins have a neuroprotective effect increasing survival of retinal ganglion cells and inhibiting astrocyte activation. In this paper LC astrocytes from human eyes LC discs from cadaveric human eyes were derived in culture. Challenge with TGFβ2 increase production of ECM proteins such as collagen and fibronectin, a response that was inhibited by both simvastatin and lovastatin. This was due to inhibition of the Smad 2/3 in the TGFβ2 signalling pathway. That statins can inhibit the fibrotic response driven by TGFβ2 in vitro suggests that these drugs may have a beneficial effect in inhibiting similar processes that lead to glaucoma.

Statins reduce TGFβ2 modulation of the extracellular matrix in cultured astrocytes of the human optic nerve head.
Kim ML, Sung KR, Shin JA, et al.
EXPERIMENTAL EYE RESEARCH
2017;164:55-63.