The porcine iodoacetic acid model of retinal degeneration: Morpho-functional characterization of the visual system

Barone, Francesca; Muscatello, Luisa Vera; Ventrella, Domenico; Elmi, Alberto; Romagnoli, Noemi; Mandrioli, Luciana; Maya‐Vetencourt, José Fernando; Bombardi, Cristiano; Mete, Maurizio; Sarli, Giuseppe; Benfenati, Fabio; Pertile, Grazia; Bacci, Maria Laura

doi:10.1016/j.exer.2020.107979

Cited by 5 publications

(16 citation statements)

References 39 publications

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“…Animals, kept at 20 ± 4 • C with a 12/12 h light/dark cycle were fed with standard swine diet (CESAC s.c.a. Conselice RA, Italy) twice a day and received water ad libitum (Barone et al, 2020). Chains and pieces of wood were used as environmental enrichment; no bedding materials were dispensed to guarantee good health conditions; every 2 days the animals received a small amount of straw as rooting material (Barone et al, 2018).…”

Section: Experimental Animals and Ethical Considerationsmentioning

confidence: 99%

“…A drop of 3% carbomer (Dacriogel, Alcon, Fort Worth, TX, United States) was applied to the inner surface of the lens electrodes to protect the cornea and to ensure good electrical contact. The International Society for Clinical Electrophysiology of Vision (ISCEV) Standards for ff-ERGs were used with the settings adjusted for the swine species, as previously described (Barone et al, 2020). We performed ff-ERG recordings using the light-adapted ERG 3.0 protocol because the retinal implant was surgically positioned in high cone density visual streak of the swine retina (Hendrickson and Hicks, 2002).…”

Section: Electrophysiological Recordingsmentioning

confidence: 99%

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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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Section: Experimental Animals and Ethical Considerationsmentioning

confidence: 99%

Section: Electrophysiological Recordingsmentioning

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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“…As each pig type has different skull and brain sizes, the implicit time of each wave varies. 4 , 6 , 61 , 62 However, the amplitudes with craniotomy were generally larger than those without craniotomy, 63 because the distance between recording elctrodes and visual cortex were shorter with craniotomy than without craviotomy. 64 Although craniotomy is an inconvenient procedure, it is helpful to record large amplitudes to rule out noise signals from true signals.…”

Section: Discussionmentioning

confidence: 98%

“… 4 , 61 Using subdermal platinum needles, Barone et al and Strain et al reported the possibility of VEP signal detection at a relatively young age without craniotomy (n2 wave just below 0.05 seconds and p2 wave just above 0.05 seconds). 6 , 62 The implicit time could be affected by the visual track length and brain size. 63 , 64 However, recording electrodes in the above two studies without craniotomy had more distance from the eye.…”

Section: Discussionmentioning

confidence: 99%

“… 1 – 3 Normative data are essential to observe the significant changes after experiments or intervention. 1 , 4 – 6 Pig and human eyes share many anatomic similarities that make the former useful in ophthalmic research. 7 , 8 The size of a pig eyeball (21.64–23.9 mm) is comparable to that of a human eyeball (23–24 mm), which is larger than those of a mouse (approximately 3 mm), rat (6–7 mm), rabbit (approximately 16 mm), and dog (18–19 mm).…”

Section: Introductionmentioning

confidence: 99%

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Normative Data of Axial Length, Retinal Thickness Measurements, Visual Evoked Potentials, and Full-Field Electroretinography in Female, Wild-Type Minipigs

Choi

Anh

et al. 2021

Trans. Vis. Sci. Tech.

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Purpose The purpose of this study was to present normative data of optical coherence tomography (OCT), electrophysiological, and ocular biometry parameters and their correlation in minipigs. Methods Eighty-eight eyes of 44 minipigs underwent full-field electroretinogram (ERG) recording and ocular biometry. However, 10 eyes of 6 minipigs were excluded because of poor OCT image quality. The thickness of the retinal sublayers was measured on a vertical line at 5 locations with a 1 mm interval from the disc margin to the dorsal periphery and at 10 locations on the visual streak. Visual evoked potentials (VEPs) were measured in 15 eyes of 8 minipigs. Results All minipigs were female with a mean age and axial length of 13.83 ± 10.56 months and 20.33 ± 0.88 mm, respectively. The implicit time of the a-wave and b-wave in scotopic 3.0 ERGs was longer than that in photopic 3.0 ERG. The implicit time of the n2-wave and p2-wave in VEP was 25.67 ± 7.41 ms and 52.96 ± 10.38 ms, respectively. The total retinal layer (TRL) and nerve fiber layer (NFL) became thinner near the periphery. The inner retinal sublayers near the visual streak were thicker than those at other locations. Central TRL and NFL thickness on visual streak was 223.06 ± 23.19 µm and 74.03 ± 13.93 µm, respectively. The temporal TRL and NFL on the visual streak were thicker than those on the nasal side. Conclusions The normative electrophysiological and OCT parameters used in our study can be used as reference data in further pig studies. Translational Relevance This study presents normative data of minipigs, which are adequate animal models for preclinical studies.

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The p-ERG spatial acuity in the biomedical pig under physiological conditions

Ventrella

Maya‐Vetencourt

Elmi

et al. 2022

Sci Rep

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Pigs are becoming an important pre-clinical animal species for translational ophthalmology, due to similarities with humans in anatomical and physiological patterns. Different models of eye disorders have been proposed, and they are good candidates to assess biocompatibility/functionality of retinal prostheses. Electroretinography is a common tool allowing to gain information on retinal function, with several types of electroretinogram (ERG) been implemented including full field (ff-ERG), multifocal (mf-ERG) and pattern (p-ERG). p-ERG represents a valuable tool to monitor Retinal Ganglion Cells (RGCs) activity and can be used to calculate p-ERG spatial acuity. Unfortunately, scarce methodological data are available regarding recording/interpretation of p-ERG and retinal acuity in biomedical pigs yet enhancing knowledge regarding pig vision physiology will allow for more refined and responsible use of such species. Aim of this study was to record p-ERG in juvenile pigs to functionally assess visual acuity. Six female hybrid pigs underwent two p-ERG recording sessions at 16 and 19 weeks of age. Photopic ff-ERG were also recorded; optical coherence tomography (OCT) and histology were used to confirm retinal integrity. ff-ERG signals were repeatable within/across sessions. All p-ERG traces consistently displayed characterizing peaks, and the progressive decrease of amplitude in response to the increment of spatial frequency revealed the reliability of the method. Mean p-ERG spatial acuities were 5.7 ± 0.14 (16 weeks) and 6.2 ± 0.15 cpd (19 weeks). Overall, the p-ERG recordings described in the present work seem reliable and repeatable, and may represent an important tool when it comes to vision assessment in pigs.

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The porcine iodoacetic acid model of retinal degeneration: Morpho-functional characterization of the visual system

Cited by 5 publications

References 39 publications

Biocompatibility of a Conjugated Polymer Retinal Prosthesis in the Domestic Pig

Biocompatibility of a Conjugated Polymer Retinal Prosthesis in the Domestic Pig

Normative Data of Axial Length, Retinal Thickness Measurements, Visual Evoked Potentials, and Full-Field Electroretinography in Female, Wild-Type Minipigs

The p-ERG spatial acuity in the biomedical pig under physiological conditions

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