Guanting Qiu

Long-term stimulation by active epiretinal implants in normal and RCD1 dogs

An epiretinal prosthesis, consisting of an extraocular microelectronic stimulator and an intraocular electrode array, was implanted in one eye of three blind and three sighted dogs. Three dogs (2 blind, 1 normal) were stimulated for 120 days, and two dogs (both normal) for 60 and 103 days respectively for 8-10 h/day at levels of 0.1 mC cm(-2) and 0.05 mC cm(-2), with each stimulus level presented to half of the array. One blind dog was kept as an inactive implant control. During the study period, electroretinograms (ERG) and fundus photographs were recorded. At the end of the study period, the dogs were sacrificed and histological and morphometric evaluation was made of the retina. No inflammatory reaction, neovascularization or hemorrhage was observed during the follow-up examinations. ERGs were unchanged. Stimulus levels used were of sufficient amplitude to elicit cortical evoked potentials. Histological evaluation showed no inflammatory infiltrates or changes in retina morphometry related to electrical stimulation when compared to the unstimulated control eye. Morphometric analysis revealed no consistent differences relating to electrical stimulation. In summary, chronic electrical stimulation of the dog retina at up to 0.1 mC cm(-2) with an epiretinal prosthesis does not appear to adversely affect the retina.

Retinal transplants evaluated by optical coherence tomography in photoreceptor degenerate rats.

Optical coherence tomography (OCT), a non-invasive method, was used for qualitative assessment of fetal retinal sheet transplants by non-invasive imaging. Rhodopsin-mutant S334ter-line-3 rats with fast retinal degeneration (28-37-day old) were transplanted with fetal retinal sheets from embryonic day (E) 18-19 pigmented normal rats. Retinal thickness measurements from transplanted (n = 51), no surgery control (n = 8), and normal pigmented rat eyes (n = 6) were obtained using a Zeiss stratus OCT-3 scanning instrument. Frozen retinal sections were stained with hematoxylin/eosin. S334ter-line-3 rats showed significant reduction in OCT retinal thickness (p<0.001) compared to normal pigmented rats at the age of 21 days. In 62% of the transplanted rats, OCT scanning revealed the presence of a subretinal graft, which was confirmed by subsequent histology. Retinal thickness in the transplant area was significantly increased compared to the area outside the transplant and to non-transplanted eyes (p<0.001). While most of the transplants with single-band OCT images (87%) had rosetted transplants, a considerable proportion of transplants having a multi-band OCT image were found to have well-laminated areas in the graft after histological evaluation. Following retinal transplantation in rodents, OCT imaging data correlated mostly with transplant morphology. OCT is a useful technique for in vivo screening and evaluation of retinal transplants. This technique determines surgical outcomes at a much earlier stage.

Nanobiolistic delivery of indicators to the living mouse retina

The development of a technique to load functional indicators into living neurons is an ongoing challenge in retinal neurophysiology. In a number of live-cell preparations, fluorescence-based indicators have been of particular importance for investigating ionic concentrations, protein localization, and other physiological parameters. In the present study, we demonstrate a novel technique that uses a modified gene gun to propel silver nanoparticles coated with indicators into live retinal neurons, and we highlight the advantages of using this technique to deliver these functional indicators.

Visual functional effects of constant blue light in a retinal degenerate rat model

Retinal degenerative conditions increase susceptibility to light damage, but rapid retinal degeneration (RD) models show less susceptibility to cyclic dim light. We investigated whether constant blue light (BL) exposure can eliminate the residual visual responses in a comparatively rapid RD rat model. Pigmented rhodopsin mutant S334ter line‐3 rat pups (21 days old) were exposed for 5–6 consecutive days to constant BL. Visual behavior was evaluated with an optokinetic head tracking apparatus. Electrophysiological recordings were made from the superior colliculus (SC). S‐antigen, red‐green opsin and rhodopsin immunoreactive residual photoreceptors were counted. Following BL exposure, head tracking was significantly reduced at 0.25 cycles degree−1 in 38‐day‐old line 3 rats. With a 0.125 cycles degree−1 stimulus, the head tracking performance of 80‐day‐old BL rats were similar to that of 220‐day‐old no–BL‐treated line‐3 rats. SC recordings also revealed a significant decrease in the residual photoreceptor activity. Histological evaluation showed reduction of the rod population in the central area of the light‐damaged retina. Exposure to constant BL considerably reduces the residual visual responses in a rapid degenerating RD rat model.