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.

中文翻译：

---

家猪共轭聚合物视网膜假体的生物相容性

视网膜光感受器的进行性退化是人类失明的最重要原因之一。共轭聚合物代表了视网膜假体领域的一个有吸引力的解决方案，并且在营养不良的皇家外科医学院 (RCS) 大鼠视网膜下植入的多层全有机假体能够挽救视觉功能。作为向人类翻译迈出的一步，我们在此报告了一种类似装置的制造和体内测试，该装置旨在适应家猪眼睛的类人尺寸，这是一种用于测试光感受器退化治疗策略的优秀动物范例。活性共轭聚合物分层在两种不同的被动基材上，即电纺丝素蛋白 (ESF) 和聚对苯二甲酸乙二醇酯 (PET)。幼稚猪的一只眼视网膜下植入有源装置，而对侧眼仅植入基质。通过体内光学相干断层扫描和全视野视网膜电图 (ff-ERG) 分析，在手术前后评估视网膜形态和功能。处死后，通过切除视网膜的免疫组织化学分析视网膜形态和炎症标志物。令人惊讶的是，基于 ESF 的假体导致增殖性玻璃体视网膜病变，植入眼中的 ff-ERG b 波消失。相比之下，基于 PET 的有源装置不会引起显着的炎症反应。正如预期的那样，由于局部光感受器损失，仅 PET 和基于 PET 的假体的视网膜下植入局部降低了外核层的厚度。然而，虽然仅植入 PET 基底降低了植入前 ERG 的 ff-ERG b 波幅度，但植入有源装置的眼睛完全保留了 ERG 响应，表明手术诱导的主动补偿光感受器损失。我们的研究结果强调了开发新一代基于共轭聚合物/PET 的假肢装置的可能性，这些假肢装置具有高度的生物相容性，并可能适用于患有退行性失明的患者的视网膜下植入。