Evaluation of viscoelastic poly(ethylene glycol) sols as vitreous substitutes in an experimental vitrectomy model in rabbits

Abstract

The aim of this study was to employ an experimental protocol for in vivo evaluation of sols of 5 wt.% poly(ethylene glycol) (PEG) in phosphate-buffered saline as artificial vitreous substitutes. A 20 gauge pars plana vitrectomy and posterior vitreous detachment were performed in the right eye of eight pigmented rabbits. Approximately 1 ml of the viscoelastic PEG sols was then injected into the vitreous space of six eyes. PEG with an average molecular weight of 300,000 and 400,000 g mol−1 was used in two and four eyes, respectively. Two eyes received balanced salt solution and served as controls. Full-field electroretinography was carried out and intra-ocular pressure (IOP, palpation) measured pre- and post-operatively at regular intervals up to 41 days. The rabbits were killed and the eyes examined by retinal photography, gross macroscopic examination and histology. The viscoelastic sols were successfully injected and remained translucent throughout the post-operative period, with some inferior formation of precipitates. None of the eyes displayed IOP elevation post-operatively, but in three of the PEG sol injected eyes transient hypotony was noted. One eye sustained retinal detachment during surgery and another two in the post-operative period. ERG recordings confirmed preservation of retinal function in three out of four eyes injected with 400,000 g mol−1 PEG. Histological examination revealed up-regulation of glial acidic fibrillary protein in Müller cells in PEG sol injected eyes, but normal overall morphology in eyes with attached retinas. The viscosity of the sol was not retained throughout the post-operative period, indicating the demand for polymer cross-linking to increase residence time. The results provide promising preliminary results on the use of PEG hydrogels as a vitreous substitute.

A new model for in vitro testing of vitreous substitute candidates

“…PEG gel elicits reactions similar to the control retinas with comparable changes in the cytoarchitecture but with earlier, more intense TUNEL labeling, consistent with previous in vivo findings [38]. In the retinal explant cultures with the longest duration (10 DIV) there was a decrease in the amount of apoptotic cells observed at earlier time points.…”

“…In two recent papers our group investigated two promising potential intravitreal substitutes in an in vivo rabbit model: Polyalkylimide (Bio-Alcamid®) [37] and a poly (ethylene glycol) (PEG) hydrogel [38].…”

“…The synthetic polymer hydrogel PEG is used in different biomedical application, has been tested for intravitreal administration of drugs [24,39] and is FDA approved for use intravitreally. The in vivo trials showed favorable biocompatibility but inadequate stability in vivo using PEG where the substance was largely tolerated with minor changes in retinal cytoarchitecture and GFAPupregulation, and minor electrophysiological changes [38]. On the other hand, Bio-Alcamid® displayed suitable physical properties but caused severe functional and morphological retinal damage with increased GFAP expression and cell death (TUNEL) [37].…”

Safety of Medium-Chain Triglycerides Used as an Intraocular Tamponading Agent in an Experimental Vitrectomy Model Rabbit

“…Various substances and approaches have been explored, but to date, clinically available alternatives to conventional tamponades (gas and silicone oil) are still very limited. [12][13][14][15][16][17][18] Identifying and developing a novel intraocular tamponading agent is a challenging task, albeit with a large therapeutical potential. The first step of this approach is to determine if the agent would be toxic to the retina or other ocular tissues.…”

A Novel Artificial Vitreous Substitute - Foldable Capsular Vitreous Body

“…Currently, a number of cross-linked polymeric hydrogels have been proposed, such as poly (vinyl alcohol) (PVA), poly poly (1-vinyl-2-pyrrolidone), poly (acrylamide) (PAA), and poly (ethylene glycol) (PEG). 2,12,[31][32][33][34] Among these, the PVA and PAA hydrogels are the most promising candidates for long-term vitreous body replacement and are highly recommended for use. They show excellent biocompatibility, are biodegradable, and can closely mimic the physico-mechanical properties of natural vitreous bodies.…”