Superior colliculus responses to light – preserved by transplantation in a slow degeneration rat model

Abstract

Purpose. To determine whether retinal transplantation can preserve visual responses in the superior colliculus (SC) of the S334ter-line-5 rat, a transgenic model for slow photoreceptor degeneration, which is more similar to human retinitis pigmentosa than the fast degeneration line 3 S334ter rat.Methods. Visual responses to a light flash were recorded in the SC. Rats that had received embryonic day (E) 19 -20 fetal retinal sheet transplants at the age of 26 -30 days were tested at the ages of 200-254 days. Controls were age-matched rats without surgery and with sham surgery. As a baseline, in no-surgery line-5 rats, the temporal pattern of visual sensitivity loss was evaluated electrophysiologically in the SC from 60 days up to one year of age.Results. In untreated S334ter-line-5 rats, decline in visual sensitivity in the SC was parallel to the photoreceptor loss. At 109 day of age, a relative scotoma developed in the area of the SC corresponding to the nasal retinal region. At 200-254 days of age, the majority of the SC was devoid of any light-driven responses. In contrast, at this time point, transplanted rats with 'good' retinal grafts with normal lamination had visual responses in the caudal region of the SC, the area corresponding topographically to the transplant location in the retina. In these rats, the various parameters of SC responses such as the latency of the onset of the visual response, the response peak amplitude and the consistency of the visual response were significantly different from the control groups (no-surgery, sham surgery, 'poor' transplants) and were more comparable to normal albino rats, however, with a slightly longer latency (70-90 vs. 30 -50 msec).Conclusions. Fetal retinal sheet transplantation showed a long-term rescue effect on visual function in this animal model of slow photoreceptor degeneration. q

BDNF-treated retinal progenitor sheets transplanted to degenerate rats: Improved restoration of visual function

“…Most of the procedures used in these experiments have been described in detail elsewhere (Sagdullaev et al, 2003;Thomas et al, 2004a;Woch et al, 2001) and are briefly described.…”

“…60 days post-surgery. For electrophysiological assessment of visual responses in the SC (Thomas et al, 2004a), rats were dark-adapted overnight and then the eyes were covered with a custom-made eye cap. After ketamine/xylazine anesthesia (see above), the gas inhalant anesthetic (1.0e2.0% halothane in 40% O 2 /60% N 2 O) was administered via an anesthetic mask (Stoelting Company, Wood Dale, IL).…”

“…Such transplants develop both inner and outer segments (Seiler and Aramant, 1998;Seiler et al, 1999), show a shift in the distribution of phototransduction proteins according to the light cycle (Seiler et al, 1999) and remain healthy for many months. In four different retinal degeneration models, such transplants have been shown to restore visual responses in the superior colliculus (SC) after long survival times of 2e8 months (Arai et al, 2004;Sagdullaev et al, 2003;Thomas et al, 2004a;Woch et al, 2001). Synaptic connectivity between transplants and host retina has been demonstrated by trans-synaptic virus tracing (Seiler et al, 2005a).…”

Vision Improvement in Retinal Degeneration Patients by Implantation of Retina Together with Retinal Pigment Epithelium

“…Human fetal donor tissue transplanted to athymic nude rats can develop retinal layers in contact with a monolayer of cotransplanted RPE. 6 Transplants of fetal retinal layers have also been shown to restore visual function in the brain in several models of retinal degeneration 7,8 and to make synaptic connections with the neural circuitry of the host retina. 9 After injecting freshly harvested retinal progenitor cells in the rho Ϫ/Ϫ mouse, increased ganglion cell responses and pupillary reflexes have been interpreted as visual improvements, 10 similar to previous results by other groups.…”

“…In different models of retinal degeneration, retinal sheet implants can restore visual responses in a small area of the superior colliculus visual center in rodents, corresponding to the placement of the graft in the retina. 7,8 Synaptic connections between subretinal implants and host retina have been demonstrated by a transsynaptic virus tracing from the host brain to the implant. 9 Two patients (Patients 2 and 10) showed improvement in both eyes, indicating a cross-over effect that could be from several causes.…”