statement: Glaucoma-on-a-chip offers the advantages of allowing controlled experimental conditions, 15 preliminary targeting of a specific cell type or pathway involved in glaucoma and investigating putative 16 neuroprotective agents prior to assessment in animal models. 17
Abstract 18We developed a glaucoma-on-a-chip (GOC) model to evaluate the viability of retinal ganglion cells (RGCs) 19 against high pressure and neuroprotective treatments. A three-layered chip consisting of interconnecting 20 microchannels and culture wells was fabricated based on simulation of physical parameters. The bottom surface of 21 the wells was mechanically modified by air plasma and coated with different membranes to model an extracellular 22 microenvironment. SH-SY5Y used as model cells to determine the best supporting membrane which was revealed 23 to be PDL/laminin. RGCs were isolated from postnatal Wistar rats and purified by magnetic assisted cell sorting up 24 to 70%. The cultured RGCs were exposed to normal (15 mmHg) or elevated pressure (33 mmHg) for 6, 12, 24, 36 25 and 48 hours, with and without adding brain-derived-neurotrophic factor (BDNF) or a novel BDNF mimetic (named 26 RNYK). RGC survival rates were 85, 78, 70, 67 and 61% under normal pressure versus 40, 22, 18, 12 and 10% under 27 high pressure at 6, 12, 24, 36 and 48 hours, respectively (P<0.0001). BDNF and RNYK reduced the rate of RGC 28 death under both normal and elevated pressures, two-fold approximately (p<0.01-0.0001). 29 42 et al., 1995; Vecino and Sharma, 2011). Without sequential treatments, the duration of IOP elevation is 43 transient in these models. Precise control over IOP elevation is difficult and certain problems may occur; these include 44 intraocular inflammation, irreversible mydriasis, IOP variability, hyphema, reduced visibility of optic discs, corneal 45 opacity, and scleral burns (Johnson and Tomarev, 2010; Rudzinski and Saragovi, 2005). While in vivo animal models 46 are indispensable to determine what events occur in live organisms, these strategies typically involve poorly defined 47 377 Acevedo, A. D., Bowser, S. S., Gerritsen, M. E. and Bizios, R. (1993). Morphological and proliferative 378 responses of endothelial cells to hydrostatic pressure: role of fibroblast growth factor. Journal of Cellular Physiology. 379 157, 603-614.
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