Functional recovery after experimental RPE debridement, mfERG studies in a porcine model

Sørensen, Nina Buus; Lassota, Nathan; Kyhn, Maria Voss; Prause, Jan Ulrik; Qvortrup, Klaus; Cour, Morten la; Kiilgaard, Jens Folke

doi:10.1007/s00417-013-2331-6

Cited by 12 publications

(25 citation statements)

References 36 publications

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“…The animals were preanesthetized and the right pupils were dilated as described previously. 13 The pigs were endotracheally intubated and artificially ventilated. Artificial ventilation was supplied with 0.5 l/min 100% oxygen and 2.5 l/min atmospheric air.…”

Section: Methodsmentioning

confidence: 99%

“…13 The animal and the respirator were electrically grounded. An infrared (IR) light emitter incorporated in the stimulation camera allowed for continuous fundus monitoring and control of the stability of “fixation.”…”

Section: Methodsmentioning

confidence: 99%

“…9 In experimental studies recordings typically last from 3 to 14 minutes. 2,3,6,10–18 The balance between the signal-to-noise ratio and the exhaustion of the examined individual determines the necessary duration of a recording. It is likely that when animals are anesthetized the noise is minimal and shorter recordings would be sufficient.…”

Section: Introductionmentioning

confidence: 99%

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Time-Dependent Decline in Multifocal Electroretinogram Requires Faster Recording Procedures in Anesthetized Pigs

Sørensen

Christiansen

Kjær

et al. 2017

Trans. Vis. Sci. Tech.

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PurposeThe time-dependent effect of anesthetics on the retinal function is debated. We hypothesize that in anesthetized animals there is a time-dependent decline that requires optimized multifocal electroretinogram (mfERG) recording procedures.MethodsConventional and four-frame global-flash mfERG recordings were obtained approximately 15, 60, and 150 minutes after the induction of propofol anesthesia (20 pigs) and isoflurane anesthesia (nine pigs). In six of the propofol-anesthetized pigs, the mfERG recordings were split in 3-minute segments. Two to 4 weeks after initial recordings, an intraocular injection of tetrodotoxin (TTX) was given and the mfERG was rerecorded as described above. Data were analyzed using mixed models in SAS statistical software.ResultsPropofol significantly decreases the conventional and global-flash amplitudes over time. The only significant effect of isoflurane is a decrease in the global-flash amplitudes. At 15 minutes after TTX injection several of the mfERG amplitudes are significantly decreased. There is a linear correlation between the conventional P1 and the global-flash DR mfERG-amplitude (R2 = 0.82, slope = 0.72, P < 0.0001). There is no significant difference between the 3-minute and the prolonged mfERG recordings for conventional amplitudes and the global-flash direct response. The global flash–induced component significantly decreases with prolonged mfERG recordings.ConclusionsA 3-minute mfERG recording and a single stimulation protocol is sufficient in anesthetized pigs. Recordings should be obtained immediately after the induction of anesthesia. The effect of TTX is significant 15 minutes after injection, but is contaminated by the effect of anesthesia 90 minutes after injection. Therefore, the quality of mfERG recordings can be further improved by determining the necessary time-of-delay from intraocular injection of a drug to full effect.Translational RelevanceGeneral anesthesia is a possible source of error in mfERG recordings. Therefore, it is important to investigate the translational relevance of the results to mfERG recordings in children in general anesthesia.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Time-Dependent Decline in Multifocal Electroretinogram Requires Faster Recording Procedures in Anesthetized Pigs

Sørensen

Christiansen

Kjær

et al. 2017

Trans. Vis. Sci. Tech.

Self Cite

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“…The goal of this in vivo preclinical study was to optimize pharmacodelivery to the macula using a well-documented pig model of CNV. 1–6 AMD is a leading cause of irreversible blindness in those over age 60 from developed countries. 7 Furthermore, neovascular AMD (nAMD) has been effectively managed in many patients by using agents that target the vascular endothelial growth factor (VEGF) protein.…”

mentioning

confidence: 99%

“…1–6 In general, fibrovascular growth extends through surgically induced defects in Bruch's membrane followed by debridement of the retinal pigment epithelium (RPE) that leads to subretinal CNV, subretinal fluid accumulation, hemorrhage, scaring, and fibrosis. 5 While not specifically an aging model, the pig model has relevance for preclinical pharmacologic studies due to the anatomic similarities between a pig and a human eye.…”

mentioning

confidence: 99%

A Pharmacodynamic Analysis of Choroidal Neovascularization in a Porcine Model Using Three Targeted Drugs

Tran

Craven

Wabner

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeTo compare the efficacy of microneedle-delivered suprachoroidal (SC) pazopanib to intravitreal (Ivit) delivery of pazopanib, bevacizumab, or a fusion protein hI-con1 versus vehicle controls on choroidal neovascularization (CNV) growth in a pig model.MethodsForty-one pigs were injected on the day of CNV induction (hI-con1 on postinduction day 14) with either 2.5 mg Ivit bevacizumab (n = 9), 1 mg Ivit pazopanib (n = 9), 300 Ivit μg hI-con1 (n = 4), or 1 mg SC pazopanib (n = 9), vs. 10 vehicle controls (3 SC + 7 Ivit = 10). Pigs were euthanized at week 2 (11), 3 (8), 4 (11), and 8 (11), and eyes were fixed for histology. The size of the CNV was determined from histology, and CNV height was the primary outcome measure. Immunostaining for cytotoxic T-cells was performed in the hI-con1 study.ResultsIn 39 of 41 (95%) eyes, type 2 CNV lesions were identified. One CNV lesion was lost during dissection. One animal was euthanized due to surgical complications. For mean CNV size comparisons, Ivit pazopanib had smaller mean height measurements (90 ± 20 μm) versus controls (180 ± 20 μm; P = 0.009), and Ivit pazopanib had smaller maximum CNV height (173 ± 43 μm) compared to SC pazopanib (478 ± 105 μm; P = 0.018). The mean lesion size in hI-con1–treated animals trended smaller than in controls (P = 0.11). Immunostaining did not detect cytotoxic T-cells.ConclusionsIntravitreal pazopanib and to a lesser extent hI-con1 reduced the size of CNV lesions. The pig model has nearly a 100% rate of type 2 CNV induction and is a reliable preclinical model with pharmacodynamics similar to humans.

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Localization, distribution, and connectivity of neuropeptide Y in the human and porcine retinas—A comparative study

Christiansen

Kiilgaard

Klemp

et al. 2018

J of Comparative Neurology

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Neuropeptide Y (NPY) is a peptide neurotransmitter abundantly expressed in the mammalian retina. Since its discovery, NPY has been studied in retinas of several species, but detailed characterization of morphology, cell-type, and connectivity has never been conducted in larger mammals including humans and pigs. As the pig due to size and cellular composition is a well-suited animal for retinal research, we chose to compare the endogenous NPY system of the human retina to that of pigs to support future research in this field. In the present study, using immunohistochemistry, confocal microscopy and 3D reconstructions, we found NPY to be expressed in GABAergic and calretinin-immunoreactive (-ir) amacrine cells of both species as well as parvalbumin-ir amacrine cells of humans. Furthermore, we identified at least two different types of medium- to wide-field NPY-ir amacrine cells. Finally, we detected likely synaptic appositions between the NPY-ir amacrine cells and melanopsin- and nonmelanopsin-ir ganglion cells, GABAergic and dopaminergic amacrine cells, rod bipolar cells, and horizontal cells, suggesting that NPY-ir cells play diverse roles in modulation of both image and non-image forming retinal signaling. These findings extend existing knowledge on NPY and NPY-expressing cells in the human and porcine retina showing a high degree of comparability. The extensive distribution and connectivity of NPY-ir cells described in the present study further highlights the potential importance of NPY signaling in retinal function.

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Functional recovery after experimental RPE debridement, mfERG studies in a porcine model

Abstract: This is the first study to show that the histological regeneration of hypopigmented RPE correlates to a return of the retinal function, measured by mfERG.

Cited by 12 publications

References 36 publications

Time-Dependent Decline in Multifocal Electroretinogram Requires Faster Recording Procedures in Anesthetized Pigs

Time-Dependent Decline in Multifocal Electroretinogram Requires Faster Recording Procedures in Anesthetized Pigs

A Pharmacodynamic Analysis of Choroidal Neovascularization in a Porcine Model Using Three Targeted Drugs

Localization, distribution, and connectivity of neuropeptide Y in the human and porcine retinas—A comparative study

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