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G.A. Silva, K.L. Kehl, K.L. Niece, S.I. Stupp; Nanoengineered Peptide Amphiphile Network for Photoreceptor Replacement in Degenerative Retinal Disorders . Invest. Ophthalmol. Vis. Sci. 2003;44(13):492.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To characterize and investigate the potential of an in situ molecularly self-assembling peptide amphiphile (PA) network for the replacement of lost photoreceptors in degenerative retinal disorders. Methods: PA molecules were chemically synthesized with the molecular formula C16H31O-A4G3EIKVAV-COOH (peptide sequence shown in bold) expressing the neurite promoting laminin peptide sequence IKVAV. These molecules were designed to self-assemble into nanoscale fibers in the presence of monovalent and divalent cations at physiological concentrations, producing a network of nanofibers that yield a stable matrix with a gel-like consistency. A 1% PA solution was microinjected into the subretinal or vitreal space of anesthetized rats and imaged using stereo microscopy. In addition, primary retinal cultures were encapsulated in vitro in IKVAV-PA gels to assess their growth and differentiation within the gels. Results: IKVAV-PA solutions injected vitreally and subretinally gelled on the order of seconds, yielding mechanically stable and firm gels in situ. The gelation process did not adversely affect the geometry of the eye, even for large injected volumes, relative to the volume of a rat eye, of up to about 100 µl. Following differing periods of time in situ, the gels were able to be surgically extracted from the eye, retaining their mechanical structure and composition. Primary dissociated retinal cultures encapsulated in vitro in PA gels under physiological conditions survived and were observed to differentiate morphologically into different distinct cell types for extended periods of time. Conclusions: PA nanofiber networks were successfully injected and gelled in intra-ocular spaces. Mixed retinal cultures encapsulated in vitro in PA gels were able to survive and differentiate. This cell/substrate system can potentially be explored as a novel delivery system for transplanting photoreceptor and/or RPE cells aimed at replacing degenerated photoreceptors in retinal degenerative disorders such as Age Related Macular Degeneration (AMD) or Retinitis Pigmentosa (RP). In addition to the mechanical role played by the PA gel, the nanofiber network expresses functional extracellular matrix (ECM) biochemical ligands, which may mimic ECM signaling cues and thus improve the clinical outcome of grafted cells for the treatment of degenerative retinal disorders.
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