Abstract
The progressive degeneration of retinal photoreceptors is one of the most significant causes of blindness in humans. Conjugated polymers represent an attractive solution to the field of retinal prostheses, and a multi-layer fully organic prosthesis implanted subretinally in dystrophic Royal College of Surgeons (RCS) rats was able to rescue visual functions. As a step toward human translation, we report here the fabrication and in vivo testing of a similar device engineered to adapt to the human-like size of the eye of the domestic pig, an excellent animal paradigm to test therapeutic strategies for photoreceptors degeneration. The active conjugated polymers were layered onto two distinct passive substrates, namely electro-spun silk fibroin (ESF) and polyethylene terephthalate (PET). Naive pigs were implanted subretinally with the active device in one eye, while the contralateral eye was sham implanted with substrate only. Retinal morphology and functionality were assessed before and after surgery by means of in vivo optical coherence tomography and full-field electroretinogram (ff-ERG) analysis. After the sacrifice, the retina morphology and inflammatory markers were analyzed by immunohistochemistry of the excised retinas. Surprisingly, ESF-based prostheses caused a proliferative vitreoretinopathy with disappearance of the ff-ERG b-wave in the implanted eyes. In contrast, PET-based active devices did not evoke significant inflammatory responses. As expected, the subretinal implantation of both PET only and the PET-based prosthesis locally decreased the thickness of the outer nuclear layer due to local photoreceptor loss. However, while the implantation of the PET only substrate decreased the ff-ERG b-wave amplitude with respect to the pre-implant ERG, the eyes implanted with the active device fully preserved the ERG responses, indicating an active compensation of the surgery-induced photoreceptor loss. Our findings highlight the possibility of developing a new generation of conjugated polymer/PET-based prosthetic devices that are highly biocompatible and potentially suitable for subretinal implantation in patients suffering from degenerative blindness.
Highlights
The development of therapeutic approaches for retinal degenerative diseases is a hot spot in vision science research (Scholl et al, 2016)
A few years ago, we reported the ability of a planar, photovoltaic, biocompatible, and fully organic retinal prosthesis to persistently restore visual functions in a rat model of progressive neuronal degeneration, the Royal College of Surgeons (RCS) rat (Antognazza et al, 2016; Maya-Vetencourt et al, 2017)
electro-spun silk fibroin (ESF) membrane used as passive substrates display at the scanning electron microscopy analysis a mesh of intermingled thin fibroin fibers (Figure 1D)
Summary
The development of therapeutic approaches for retinal degenerative diseases is a hot spot in vision science research (Scholl et al, 2016). The wide variety of genetic defects causing retinal degeneration poses some challenges for the development of therapeutic approaches. Among them are strategies that aim at rescuing vision by using electronic devices able to stimulate spared retinal networks (Walter et al, 2005; DeMarco et al, 2007; Gerding et al, 2007; Yanai et al, 2007; Zrenner et al, 2011; Mathieson et al, 2012; Mandel et al, 2013; Ayton et al, 2014; Lorach et al, 2015). The optimization of the current retinal prostheses is necessary to restore high-quality visual capabilities in dystrophic patients
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