Functional implications of short‐term retinal detachment in porcine eyes: study by multifocal electroretinography

Abstract

ABSTRACT.Purpose: The aim of the study was to determine the type and magnitude of detectable changes in pig multifocal electroretinography (mfERG) induced by the vitreoretinal surgical procedures necessary to gain access to the subretinal space.Methods: Twenty pigs underwent posterior segment surgery. Six animals had a vitrectomy (V), six had in addition a retinal bleb detachment (V + B); five had in addition a retinal diathermia on the bleb (V + B + D) and three received a retinotomy in the diathermized retinal area (V + B + D + R). mfERG evaluation was performed at baseline and 1 and 6 weeks postoperatively. Selected eyes were enucleated for histological evaluation. Results:The retinal detachments blebs all reattached spontaneously. All four surgical sequences resulted in slight, non-significant changes in the mfERG peaks. A trend towards an amplitude reduction of the mfERG peaks N1, P1 and N2 were observed within the first postoperative week. After 6 weeks, all amplitudes had normalized. Of the implicit times only that of peak N1 (after retinal diathermia) was prolonged significantly at 1 week (P ¼ 0.037). However, it returned to the preoperative level after 6 weeks. Histologically, the retinal detachment bleb was characterized by transient double layering of the retinal pigment epithelium (RPE) and loss photoreceptor outer segments.Conclusion: Access to the subretinal space in pigs can be gained without permanent detectable changes in the mfERG. A short-term retinal detachment was found to cause only reversible electrophysiological and histological changes in the outer retina, which suggests that this procedure is tolerated well in the porcine retina. The size of the known destructive lesion (retinotomy) was too small to be detected, given the spatial resolution of the mfERG method applied. In the future, the presented protocol can be used to assess the functional outcome of surgery and transplantation in the subretinal space in pigs.

Functional and Anatomic Consequences of Subretinal Dosing in the Cynomolgus Macaque

“…By 3 months, the RMS amplitudes and P1 latencies had recovered to normal or nearly normal levels. Consistent with our study, Kyhn et al in a study of subretinal injections in porcine eyes showed return of retinal mfERG function after 6 weeks of reattachment 48 .…”

Iodoacetic acid, but not sodium iodate, creates an inducible swine model of photoreceptor damage

“…Artificial tears were applied every 2 – 3 minutes to keep the cornea and electrode moist. Similar to previously published methods (Kyhn et al, 2008; Moren et al, 2010) a VERIS System, (Electrodiagnostic, Inc.) was used to record the mfERG. This includes a fundus camera that produces a hexagonal stimulus pattern and simultaneously allows real-time viewing of the pattern on the retina providing feedback of stimulus location relative to the optic disc and retinal blood vessels.…”

An Innovative Surgical Technique for Subretinal Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigmented Epithelium in Yucatan Mini Pigs: Preliminary Results

“…However, it may be considered a potential limitation of our study that we did not prospectively examine retinal response using multifocal electroretinography (mfERG). Christiansen et al elaborated this sensitive technique and were able to provide reliable data on the electrophysiologic dependencies of different subretinal materials [18,27]. Although we had no robust mfERG setup in place and would endorse including mfERG in future studies, we feel confident regarding the biocompatibility of the material with and without cells due to our experience with the optokinetic nystagmus and superior colliculus recordings in the RCS rat (data submitted to FDA with an Investigational New Drug submission; this aspect is also discussed in a recent review article by our group [28]).…”

“…The study was also limited by the time frame; testing over a longer follow-up period would have been more informative. We experimented with using multifocal electroretinography, different from the type used by Kyhn et al in a pilot surgery [18], but encountered too much noise to obtain reliable in vivo data. Overall, we believe that a sustained and successful RPE transplantation mandates the safe transplantation of a polarized monolayer to physiologically achieve or maintain visual acuity and avoid cell death over time.…”

“…RPE transplantation in the pig is a relatively young field, and surgical implications of such implantations have not been fully explored [14][15][16][17][18][19][20][21]. Human autologous RPE transplantation studies, primarily in patients with exudative AMD, have shown that intraoperative complications are infrequent [22][23][24].…”