Encapsulated cell-based intraocular delivery of ciliary neurotrophic factor in normal rabbit: dose-dependent effects on ERG and retinal histology.
OBJECTIVE
ERG and histologic changes were investigated in normal rabbits after intravitreal implantation of encapsulated cell technology (ECT) devices releasing ciliary neurotrophic factor (CNTF).


METHODS
Fifteen adult New Zealand White albino rabbits had ECT devices secreting CNTF at 22, 5, or 0 ng/d implanted in the superior temporal quadrant of the left eye. The low dose has been shown to produce substantial rescue of photoreceptors in the rcd1 canine model of retinal degeneration. Right eyes were untreated. Ganzfeld dark- and light-adapted ERGs and clinical observations were performed at 5, 15, and 25 days after implantation. Rod a-waves and rod and cone b-waves and outer nuclear layer (ONL) morphology were evaluated at 25 days.


RESULTS
Clinical examination showed minimal changes in a few CNTF-treated eyes, including vitreous membranes and engorgement of iris vessels at day 25. Retinas appeared normal. CNTF did not significantly affect the rod a- or b-waves, although the b-wave amplitude tended to be larger in CNTF-treated retinas at low flash intensities. The cone b-wave amplitude was significantly reduced in high-dose eyes at some flash intensities. The ONL area in high-dose eyes was significantly greater because of increased thickness than in fellow retinas. ONL cell size was significantly increased, and staining density decreased in CNTF-treated retinas.


CONCLUSIONS
CNTF, given by intravitreal ECT device at doses that protect photoreceptors in a canine model of retinal degeneration (5 ng/d), did not adversely affect either rod or cone ERG function of normal rabbit retina. The cone ERG was more sensitive to suppression being reduced, at low flash intensities, by 22 ng/d. Dose-related changes in the ONL and photoreceptor cell nuclei did not represent a toxic effect, because they were not associated with deficits in the rod ERG over a broad range of intensities.
Bush
Ronald A
RA
Department of Ophthalmology and Visual Science, Kellogg Eye Center, University of Michigan, Ann Arbor, USA. bushr@nidcd.nih.gov
Lei
Bo
B
Tao
Weng
W
Raz
Dorit
D
Chan
Chi-Chao
CC
Cox
Terry A
TA
Santos-Muffley
Maria
M
Sieving
Paul A
PA
D000818:Animals; D020934:Ciliary Neurotrophic Factor / Q000008:administration & dosage*; D003623:Dark Adaptation; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004343:Drug Implants; D004596:Electroretinography / Q000187:drug effects*; D010775:Photic Stimulation; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000473:pathology* / Q000502:physiology; D014822:Vitreous Body
D020934:Ciliary Neurotrophic Factor; D004343:Drug Implants