Cytokines are cell-signaling proteins that mediate diverse physiological processes. They also play a crucial role in various inflammatory processes, as well as in wound healing and fibrotic scarification.
1 Fibrosis is a process that is characterized by an exuberant formation of connective tissue, which entails the production of collagens and glycosaminoglycans by activated fibroblasts. In the retina, tissue-resident cells, such as glia and macrophages, initiate fibrosis by the release of soluble factors,
2,3 among which TGF-β is one of the best characterized.
1,4 Other profibrotic mediators include the platelet-derived growth factor (PDGF), IL-4, IL-6, IL-13.
1,2,5 All of these cytokines stimulate the production and deposition of collagen by fibroblasts and promote their activation and differentiation into myofibroblasts.
1,2,5 Müller glial cells are known to activate fibroblasts and to promote fibrotic changes within the eye, such as proliferative vitreoretinopathy (PVR)
3,6 and the formation of epiretinal membranes (ERMs).
7,8 Epiretinal membranes are characterized by the growth of fibrocellular tissue along the inner limiting membrane (ILM), which can lead to metamorphopsia and visual loss. The most frequently encountered, so-called idiopathic ERMs, are not linked to any other ocular disease process and their pathogenesis remains unidentified. Macular holes (MHs), on the other hand, are full-thickness foveal defects, extending from the ILM to the RPE. The release of vitreomacular traction (VMT) as the underlying pathomechanism of idiopathic macular holes
9,10 leads to degenerative and atrophic changes, including the formation of prominent, cystoid spaces at the edge of the MH, which may result in its enlargement without detectable scar formation in more than 50% of the cases.
11,12 In the remaining instances, a horizontal traction, which is represented by a hyperreflective band in optical coherence tomography on the inner retinal surface with or without wrinkling of the retina, is visible. This phenomenon is probably the consequence of either ILM-contraction or of the formation of a thin ERM. In these cases, enlargement of the MH, resulting from both a contraction of the ERM and atrophic changes, is to be expected.
13