June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Intraocular Delivery of Ciliary Neurotrophic Factor (CNTF) by Encapsulated Cell Technology Implants Restores Cone Function and Day Vision in Dogs with CNGB3-Achromatopsia
Author Affiliations & Notes
  • Andras Komaromy
    Small Animal Clinical Studies, Michigan State Univ, Coll of Vet Med, East Lansing, MI
    Clinical Studies, Univ Pennsylvania, School of Vet Med, Philadelphia, PA
  • Kristin Koehl
    Small Animal Clinical Studies, Michigan State Univ, Coll of Vet Med, East Lansing, MI
  • Christine Harman
    Small Animal Clinical Studies, Michigan State Univ, Coll of Vet Med, East Lansing, MI
  • Pam Heatherton
    Neurotech Pharmaceuticals, Inc., Cumberland, RI
  • Konrad Kauper
    Neurotech Pharmaceuticals, Inc., Cumberland, RI
  • Gustavo Aguirre
    Clinical Studies, Univ Pennsylvania, School of Vet Med, Philadelphia, PA
  • Weng Tao
    Neurotech Pharmaceuticals, Inc., Cumberland, RI
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1718. doi:
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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)

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Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: 490 cytokines/chemokines • 615 neuroprotection • 689 retina: distal (photoreceptors, horizontal cells, bipolar cells)  
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