Hyaluronic Acid‐Based Hydrogels Enable Rod Photoreceptor Survival and Maturation In Vitro through Activation of the mTOR Pathway. (3rd February 2016)

• Record Type: Journal Article
• Authors: Mitrousis, Nikolaos; Tam, Roger Y.; Baker, Alexander E. G.; van der Kooy, Derek; Shoichet, Molly S.
• Is Part Of: Advanced functional materials. Volume 26:Number 12(2016)
• Page Start: 1975
• Page End: 1985
• Publication Date: 2016-02-03
• Subjects: hyaluronic acid -- mTOR -- photoreceptor -- tissue engineering; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.201504024
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract : The culture of isolated photoreceptors in vitro has remained elusive in ­neuroscience. By using defined hyaluronic acid (HA) hydrogels, photo­receptor survival and maturation in vitro is dramatically increased, as evidenced by upregulation of outer segment markers at the RNA and protein levels. While substrate stiffness is known to be a key factor influencing cell survival in vitro, it is shown that isolated photoreceptors do not respond to modifications in hydrogel stiffness modifications but depend, instead, on HA for survival. While the molecular pathways that are induced by HA on photoreceptors are unknown, mTOR activation is identified as the molecular mechanism underlying the pro‐survival effect, and it is demonstrated that the canonical Wnt and RhoA pathways are intermediaries. This work establishes a valuable method for isolated photoreceptor culture in vitro, which will be useful in translational and basic retinal research. The pathways identified herein may be useful targets in retinal degeneration. Abstract : A hydrogel that can maintain isolated photoreceptors alive in vitro is developed. Toward deciphering its mechanism of action, stiffness and hyaluronic acid presence are investigated. This platform can be used for basic and translational research.