Cord blood serum (CBS) reduces the expression of GFAP and inflammatory cytokines in retinal Muller cells under stress damage

Abstract

Purpose Human cord blood serum (CBS) is enriched with neurotrophins endowed of neuroprotective functions. Muller cells orchestrate retinal functioning, but their hyper‐activation can exacerbate retinal damage under oxidative stress, which typically occurs during neurodegenerative diseases. In this study we tested whether CBS could regulate human Muller cell activation under H2O2‐ and IL‐1□‐ induced damage. Methods Selected neurotrohpins (BDNF, TGF‐□, NGF, GDNF, EGF) were analysed in CBS (Human Magnetic Luminex Screening Assay). The human Muller cell line Moorfields/Institute of Ophtalmology‐Muller 1 (MIO‐M1) was obtained from the UCL Institute of Ophtalmology, London, UK1. MIO‐M1 were seeded in growth media enriched with standard FBS or CBS, both at 5%. After 24 h, MIO‐M1 were exposed to H2O2 and IL‐1□ for 24 h. CBS effects were compared to FBS control cells in terms of cell survival (MTT assay), activation (GFAP mRNA) and inflammation (TNF‐□ and IL‐6 mRNA). Results Median levels of neurotrophins in CBS were: BDNF 1.5 ng/ml, NGF 3.0 pg/ml, GDNF 1.5 pg/ml, TGF‐□ 36.3 pg/ml, EGF 820 pg/ml. MIO‐M1 pre‐cultured with CBS and exposed to H2O2, underwent a 50% decrease of GFAP mRNA in comparison to FBS control cells. CBS also mitigated the inflammatory activation, as shown by a significant 50% reduction of IL‐6 and TNF‐□ mRNA levels. The CBS ability to modulate the inflammatory pathway was confirmed by the significant decrease of IL‐6 and TNF‐□ genes (6‐ and 4‐ fold lower than FBS, respectively) in MIO‐M1 exposed to IL‐1□ (50 ng/ml). Conclusion CBS protects retinal Muller cells from damage under in vitro stress conditions. The main targets of this neuroprotecting stretegy are GFAP, marker of Muller cell activation, and the inflammatory cytokines, closely related to the neurodegenerative diseases. Therefore, CBS represents a promising therapeutic agent for the neurodegenerative diseases and further studies are necessary to validate this issue. Reference Limb GA et al. 2002, IOVS, 43; 864–869.