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CNGB3-Achromatopsia Clinical Trial With CNTF: Diminished Rod Pathway Responses With No Evidence of Improvement in Cone Function
- Source :
- Investigative ophthalmology & visual science, vol 55, iss 10
- Publication Year :
- 2014
- Publisher :
- Association for Research in Vision and Ophthalmology (ARVO), 2014.
-
Abstract
- Purpose Ciliary neurotrophic factor (CNTF) protects rod photoreceptors from retinal degenerative disease in multiple nonhuman models. Thus far, CNTF has failed to demonstrate rod protection in trials for human retinitis pigmentosa. Recently, CNTF was found to improve cone photoreceptor function in a canine CNGB3 achromatopsia model. This study explores whether this finding translates to humans with CNGB3 achromatopsia. Methods A five-subject, open-label Phase I/II study was initiated by implanting intraocular microcapsules releasing CNTF (nominally 20 ng/d) into one eye each of CNGB3 achromat participants. Fellow eyes served as untreated controls. Subjects were followed for 1 year. Results Pupil constriction in treated eyes gave evidence of intraocular CNTF release. Additionally, scotopic ERG responses were reduced, and dark-adapted psychophysical absolute thresholds were increased, attributable to diminished rod or rod pathway activity. Optical coherence tomography revealed that the cone-rich fovea underwent structural changes as the foveal hyporeflective zone (HRZ) became diminished in CNTF-treated eyes. No objectively measurable enhancement of cone function was found by assessments of visual acuity, mesopic increment sensitivity threshold, or the photopic ERG. Careful measurements of color hue discrimination showed no change. Nonetheless, subjects reported beneficial changes of visual function in the treated eyes, including reduced light sensitivity and aversion to bright light, which may trace to decreased effective ambient light from the pupillary constriction; further they noted slowed adaptation to darkness, consistent with CNTF action on rod photoreceptors. Conclusions Ciliary neurotrophic factor did not measurably enhance cone function, which reveals a species difference between human and canine CNGB3 cones in response to CNTF. (ClinicalTrials.gov number, NCT01648452.).
- Subjects :
- Male
Time Factors
Achromatopsia
genetic structures
CNGB3
Color Vision Defects
Ciliary neurotrophic factor
ECT implant
Eye
Ophthalmology & Optometry
Medical and Health Sciences
chemistry.chemical_compound
Retinal Rod Photoreceptor Cells
CNTF-releasing implant
CNTF
cone photoreceptor
Prospective Studies
Tomography
human clinical trial
Drug Implants
medicine.diagnostic_test
biology
Articles
Biological Sciences
Middle Aged
Sensory Systems
Rod Photoreceptors
Female
achromatopsia
Tomography, Optical Coherence
Photopic vision
rod photoreceptor
Adult
medicine.medical_specialty
Cyclic Nucleotide-Gated Cation Channels
Capsules
Dark Adaptation
Cellular and Molecular Neuroscience
Young Adult
Clinical Research
Ophthalmology
Retinitis pigmentosa
Electroretinography
medicine
Humans
Letters
Ciliary Neurotrophic Factor
Scotopic vision
Eye Disease and Disorders of Vision
business.industry
Neurosciences
Retinal
medicine.disease
Cone (formal languages)
eye diseases
chemistry
Optical Coherence
biology.protein
sense organs
business
Follow-Up Studies
Subjects
Details
- ISSN :
- 15525783
- Volume :
- 55
- Database :
- OpenAIRE
- Journal :
- Investigative Opthalmology & Visual Science
- Accession number :
- edsair.doi.dedup.....80569c46fcc3a2d3730381907677b7a1