A Self-Assembling Peptide Gel as a Vitreous Substitute: A Rabbit Study

Abstract

Citation: Uesugi K, Sakaguchi H, Hayashida Y, et al. A self-assembling peptide gel as a vitreous substitute: a rabbit study. Invest Ophthalmol Vis Sci. 2017;58:4068-4075. DOI: 10.1167/iovs.17-21536 PURPOSE. To evaluate a self-assembling peptide gel as a potential vitreous substitute.METHODS. PanaceaGel SPG-178, a self-assembling peptide gel, was diluted with distilled water and a balanced salt solution to achieve a final peptide concentration of 0.1%. The gel's refractive index, visible light transmission rate, and rheologic properties were investigated. The gel's biocompatibility was evaluated by examining the cellular viability (live and dead staining) and proliferation rate (alamarBlue assay). A 25-G pars plana vitrectomy was performed on the right eye of 21 New Zealand white rabbits. The gel was then injected into the vitreous cavity of 15 eyes. Six eyes were injected with a balanced salt solution (BSS) and served as controls. Toxicity was examined using electroretinography and histologic analysis after the injection of the gel.RESULTS. The gel's physical properties closely resembled those of human vitreous. The gel showed no apparent toxicity. When the gel was injected into the vitreous cavity, fragmentation was not observed. Additionally, the gel remained transparent in the vitreous cavity and no complications were observed for 3 months after the injection. Electroretinography and histology confirmed the gel's biocompatibility.CONCLUSIONS. This diluted self-assembling peptide gel could be provide a promising vitreous substitute.Keywords: vitreous humor, retina, self-assembling peptide gel T he vitreous is located in the posterior segment of the eye and fills approximately two-thirds of the globe. It is a waterbased hydrogel containing collagen and hyaluronic acid. It also plays an important role in the pathophysiology for some vitreoretinal diseases, including retinal detachment and macular hole. 1,2To treat these diseases, the vitrectomy is an important procedure, and the use of vitreous substitute is necessary. The aim of its use is to not only provide an organic substitute to recover IOP and eyeball volume but to also supply a functional substitute for retinal reattachment. Air, expandable gas, and silicone are currently used as vitreous substitutes. However, air and expandable gas are not suitable long-term substitutes due to their absorption. A silicone substitute must be removed from the eye after a specific period of time because its toxicity can lead to complications, including glaucoma and cataracts. Because of their hydrophobic properties of these substitutes, the eye is not completely filled and growth factors can accumulate in the unfilled spaces. This may also lead to postoperative complications, including development of proliferative membranes. [4][5][6] Recently, several studies have examined both natural 7-13 and synthetic 2,14-20 hydrophilic polymers as vitreous substitutes. These polymers do not have limitations related to hydrophobicity, but other problems may be observed. Hydrogels ...

Macro- and Microscale Properties of the Vitreous Humor to Inform Substitute Design and Intravitreal Biotransport

“…A big discrepancy in the number of publications on hydrogel vitreous substitutes and vitreous humor in the years 1995-2000 (9 publications and 0 publications, respectively) should be noted, considering the approval of silicone oil for use as a vitreous substitute by the Food and Drug Administration (FDA) in 1994. 58 Synthetic 33,34,59-91 and semisynthetic [92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108] hydrogels have been more common materials for experimental vitreous substitutes in recent years, while natural hydrogels 37,[109][110][111][112][113][114][115][116][117][118][119][120][121][122][123] were much more prevalent in the early years ( Figure 3B). The foldable capsular vitreous body (FCVB) is a different polymeric design for a vitreous substitute that is currently undergoing clinical trials in China.…”

“…However, stiff hydrogels can be difficult to inject through a small gauge needle into the vitreous chamber. The storage and loss moduli of synthetic hydrogels 34,[59][60][61][62]69,73,74,76,[81][82][83] (G' = 1203 ± 755 Pa, n = 18 and G" = 373 ± 330 Pa, n = 12) and semisynthetic hydrogels [92][93][94]97,98,[100][101][102]104 (G' = 1330 ± 1090 Pa, n = 9 and G" = 291 ± 223 Pa, n = 9) are approximately two orders of magnitude higher, while natural hydrogels' 37,110 (G' = 99.4 ± 53.4 Pa, n = 3 and G" = 51.5 ± 48.5 Pa, n = 2) are about one order of magnitude higher compared to the human vitreous [15][16][17] (G' = 5.09 ± 1.86 Pa, n = 3 and G" = 1.81 ± 0.98 Pa, n = 3). Hydrogels with different mechanisms of injection into the eye also have a wide variation in storage and loss moduli ( Table 5 and Figure 4B).…”

Assessment of a self-assembling peptide gel, SPG-178, in providing a clear operative field for trabeculectomy surgery for glaucoma in an animal model

“…3f). The reason for the cloudiness of the SPG-178 in the anterior chamber is believed to be because of an aggregation caused by the electrostatic interaction between charged SPG-178 and sodium, chloride, and protein in the aqueous humor 14 . The SPG-178 that was attached to the surface of the corneal endothelium was turbid and white in colour and kept its shape until five weeks after the operation (Fig.…”

“…SPG-178 is neutral and transparent, and when it comes into contact with salt or a bodily fluid such as blood, it forms a boundary 4 as it hardens 11 . These characteristics have been studied in various medical fields [12][13][14][15] . Taking advantage of the unique properties of the SPG-178, herein we report its use to ensure intraoperative visibility applicable to a wide range of ophthalmic operations, not least of which is surgery for glaucoma that, as mentioned, is prone to excessive bleeding.…”

Mechanical Characteristics of SPG-178 Hydrogels: Optimizing Viscoelastic Properties through Microrheology and Response Surface Methodology

“…SPG-178 is the most recently introduced SApeptides with the amino acid sequence of [CH 3 CONH]-RLDLRLALRLDLR-[CONH 2 ] (R, L, D, and A indicate arginine, leucine, aspartic acid, and alanine, respectively), forming a fibrillar hydrogel structure via the self-assembling process, similar to RADA16 [11] . SPG-178 hydrogel has potential applications in tissue engineering, including vitreous substitute for eyes [12] , bone regeneration [13,14] , neurite outgrowth of the spinal motor neurons [15] , and rapid hemostasis [16] . Due to its neutral pH value in water as well as its resistance to autoclaving conditions, SPG-178 is easier to handle in comparison to RADA16-I.…”