Differential effects of TGF‐β and FGF‐2 on in vitro proliferation and migration of primate retinal endothelial and Müller cells

Abstract

. Purpose: During retinal development, the pattern of blood vessel formation depends upon the combined effects of proliferation and migration of endothelial cells, astrocytes and Müller cells. In this study, we investigated the potential for transforming growth factor‐β (TGF‐β) and fibroblast growth factor (FGF‐2) to influence this process by regulating proliferation and migration of retinal endothelial and macroglial cells. Methods: We assessed the effects of exogenous TGF‐β and FGF‐2 on the proliferation and migration of cultured endothelial (RF/6A) and Müller cell (MIO‐M1) lines. Cell proliferation was measured using a MTT [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) colorimetric assay over 72 hr. Cell migration was measured using a scratch‐wound assay over 72 hr. Results: Transforming growth factor‐β inhibited the proliferation of endothelial and Müller cells and inhibited the migration of Müller cells, but not endothelial cells, compared to untreated controls. Conversely, FGF‐2 increased endothelial cell proliferation but inhibited endothelial cell migration. Fibroblast growth factor‐2 increased migration of Müller cells but had little effect on proliferation except at higher concentrations (20 ng/ml). Conclusion: Taken together, these observations indicate that TGF‐β and FGF could work in concert to inhibit endothelial cell proliferation and migration, respectively; this may have implications for establishing and maintaining the avascular zone of primate fovea.

Transforming growth factor beta 1 induces CXCL16 and leukemia inhibitory factor expression in osteoclasts to modulate migration of osteoblast progenitors

“…TGF-β was reported to enhance migration in both transformed and normal cells, including osteoblastic cells [10–18]. However, there are reports that TGF-β can also inhibit migration of normal and transformed cells, indicating complex and potentially tissue-specific influences of TGF-β on migration [19–21]. Tang et al [18] documented that TGF-β released during bone resorption is a chemotactic agent that recruits mesenchymal cells to the sites of resorption to begin the replacement phase of bone turnover.…”

Activated α 2 ‐macroglobulin induces Müller glial cell migration by regulating MT1‐MMP activity through LRP1

“…In the retina, MGCs play key structural and functional roles, and under physiological conditions these cells have a limited capability to migrate and proliferate. Nevertheless, in determined pathological abnormalities, MGCs can undergo functional and phenotypic changes, thereby acquiring the ability to migrate toward injured sites to promote retinal remodeling and cellular repopulation (41, 47). Although the regulatory mechanisms that promote this MGC migration are unclear, it has been proposed that ECM remodeling, produced by MMP‐2 and MMP‐9, may facilitate and induce the cellular migration of MGCs (22, 48).…”

“…In contrast, LRP1 reduction in MIO-M1 cells did not interfere with the cellular migration induced by the fibroblast growth factor 2 (FGF-2; ref. 41). Thus, we conclude that ␣ 2 M*-promoted MIO-M1 cell migration is mediated by LRP1.…”

IGF-1 Regulates the Extracellular Level of Active MMP-2 and Promotes Müller Glial Cell Motility

“…In the retina, under certain pathologic abnormalities, MGC can undergo functional and phenotypic changes, thereby acquiring the ability to migrate toward injured sites to promote retinal remodeling and cellular repopulation. 73,74 In addition, it has been demonstrated that the humanderived MGC line, termed MIO-M1, exhibits stem cell properties and may be used for neuronal regeneration within mammalian retina. 38,75 Although these transplanted cells showed an acceptable integration, survival, and neural differentiation in animal retinas with neurodegenerative damage, the success of cellular therapy was relatively poor due to the absence of migratory properties.…”