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Andras Komaromy, Kristin Koehl, Christine Harman, Pam Heatherton, Konrad Kauper, Gustavo Aguirre, Weng Tao; Intraocular Delivery of Ciliary Neurotrophic Factor (CNTF) by Encapsulated Cell Technology Implants Restores Cone Function and Day Vision in Dogs with CNGB3-Achromatopsia. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1718.
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© ARVO (1962-2015); The Authors (2016-present)
We have previously demonstrated in dogs with CNGB3-achromatopsia that intravitreal bolus injection of CNTF (1) resulted in transient restoration of cone function and day vision, and (2) optimized long-term cone functional response to AAV-mediated gene augmentation therapy. The objective of this study was to determine if sustained intravitreal delivery of CNTF by encapsulated cell technology (ECT) could reverse the disease phenotype of CNGB3-achromatopsia in dogs long-term.
Dogs homozygous for the D262N missense mutation in CNGB3 were unilaterally implanted with CNTF-secreting, encapsulated cell implants. The pre-implant CNTF secretion rate was 15 ng/day. The animals were 3 months (n=2) and 27 months (n=1) of age and were day blind with no recordable cone ERG prior to surgery. Following implant placement, the dogs were examined weekly by standard full-field electroretinography under general anesthesia and visual behavioral testing in an obstacle avoidance course.
In the operated eyes, day vision and cone function were partially restored by 1 week following CNTF-implant placement. The amplitudes of single and flicker cone ERG responses were small (~5-10% of normal) but were maintained for at least 5 weeks thus far. Scotopic ERG responses were reduced in 2 of the 3 implanted eyes to <30% of amplitudes recorded in the non-operated fellow eyes. These ERG data were comparable to our observations following single intravitreal bolus injection of 12 μg CNTF.
Sustained intravitreal delivery of CNTF by ECT rescues cone function and day vision in CNGB3-achromatopsia. It remains to be shown if this therapeutic effect can be sustained long-term and if ECT can be combined with AAV-mediated cone-directed gene augmentation to optimize treatment.
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