Subretinally injected semiconducting polymer nanoparticles rescue vision in a rat model of retinal dystrophy

Maya‐Vetencourt, José Fernando; Manfredi, Giovanni; Mete, Maurizio; Colombo, Elisabetta; Bramini, Mattia; Marco, Stefano Di; Shmal, Dmytro; Mantero, Giulia; Dipalo, Michele; Rocchi, Anna; DiFrancesco, Mattia L.; Papaleo, Ermanno D.; Russo, Angela; Barsotti, Jonathan; Eleftheriou, Cyril G.; Maria, Francesca Di; Cossu, Vanessa; Piazza, Fabio; Emionite, Laura; Ticconi, Flavia; Marini, Cecilia; Sambuceti, Gianmario; Pertile, Grazia; Lanzani, Guglielmo

doi:10.1038/s41565-020-0696-3

Cited by 142 publications

(192 citation statements)

References 60 publications

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“…Several retinal prosthetics have demonstrated promising clinical outcomes [4][5][6][7] yet even the best restored visual acuity (20/460) [7] has been still limited to be below the visual acuity of legal blindness (20/200). Recently, various research groups have introduced new designs of microelectrodes [8][9][10][11] and/or new materials such as nanowires [12] and nanoparticles [13] to further improve the spatial resolution of retinal implants. In addition to those engineering efforts, it is critical to make electrically-elicited neural activities created by retinal implants similar to visually-elicited neural activities created by the healthy retina for improved artificial vision [1,14,15].…”

Section: Introductionmentioning

confidence: 99%

Electric Stimulation Elicits Heterogeneous Responses in ON but Not OFF Retinal Ganglion Cells to Transmit Rich Neural Information

Kang

Jang

Kim

et al. 2021

IEEE Trans. Neural Syst. Rehabil. Eng.

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Section: Introductionmentioning

confidence: 99%

Electric Stimulation Elicits Heterogeneous Responses in ON but Not OFF Retinal Ganglion Cells to Transmit Rich Neural Information

Kang

Jang

Kim

et al. 2021

IEEE Trans. Neural Syst. Rehabil. Eng.

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“…Not only sensitivity to light significantly increased, but also spatial resolution and metabolic activity of the visual cortex were positively affected. More recently, we developed a secondgeneration nanoscale prosthesis that similarly reinstates visual functions in dystrophic RCS animals (Benfenati and Lanzani, 2018;Maya-Vetencourt et al, 2020). In the present work, we directed our efforts toward the transfer of the initial results obtained in rodents to the swine model, as a preliminary step before phase-1 experimentation in humans.…”

Section: Introductionmentioning

confidence: 99%

Biocompatibility of a Conjugated Polymer Retinal Prosthesis in the Domestic Pig

Maya‐Vetencourt

Marco

Mete

et al. 2020

Front. Bioeng. Biotechnol.

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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.

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“…Recently, Lanzani and Benfenati's groups unveiled the first "liquid retina device" consisting of a water suspension of single‐component P3HT‐NPs without the need for solid support, wiring, or external cameras (Figure 7). 106 It has been demonstrated that once P3HT‐NPs are microinjected into the eye of blind rats, with a minimally invasive procedure, they are distributed throughout the subretinal space without causing trophic effects on the residual photoreceptors or significant inflammatory reactions (Figure 7A,B). Remarkably, NPs bestow inner retinal neurons with light sensitivity (Figure 7C,D).…”

Section: Biological Applications Of Pt‐npsmentioning

confidence: 99%

“…Quantification of the pupillary constriction as a function of light intensity in RCS‐rdy, RCS, RCS + P3HT‐NPs, and RCS + glass NPs rats (H). Reproduced from reference 106 with permission from Springer Nature, Copyright 2020…”

Section: Biological Applications Of Pt‐npsmentioning

confidence: 99%

Synthesis, characterization, and biological applications of semiconducting polythiophene‐based nanoparticles

Zangoli

Maria

2020

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In recent years, polythiophene‐based nanoparticles (PT‐NPs) have attracted increasing attention because of their outstanding characteristics deriving from a wealth of properties such as charge conduction in the oxidized/reduced states, light absorption/emission at an appropriate wavelength, geometrical adaptability, thermal and chemical stability, and solubility in common solvents. Furthermore, the great synthetic flexibility of the thiophene core has allowed the engineering of a multitude of nanomaterials with made‐to‐order properties. This review is focused on the synthesis and characterization of aqueous PT‐NPs and their biological applications. In particular, both in vitro and in vivo bioapplications will be presented, in which thiophene‐based nanomaterials act as photoactuators, that is, as exogenous components capable of transforming a primary stimulus of light into a highly spatiotemporally resolved secondary stimulus able to alter cell's physiological functions. Furthermore, examples of applications of PT‐NPs in biomedicine, such as photodynamic therapy and photothermal therapy, will be discussed.

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Subretinally injected semiconducting polymer nanoparticles rescue vision in a rat model of retinal dystrophy

Cited by 142 publications

References 60 publications

Electric Stimulation Elicits Heterogeneous Responses in ON but Not OFF Retinal Ganglion Cells to Transmit Rich Neural Information

Electric Stimulation Elicits Heterogeneous Responses in ON but Not OFF Retinal Ganglion Cells to Transmit Rich Neural Information

Biocompatibility of a Conjugated Polymer Retinal Prosthesis in the Domestic Pig

Synthesis, characterization, and biological applications of semiconducting polythiophene‐based nanoparticles

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