Abstract | PURPOSE: The objective of the present study was to evaluate the therapeutic efficacy of ciliary neurotrophic factor ( CNTF) delivered through encapsulated cells directly into the vitreous of the eye in an rcd1 canine model of retinitis pigmentosa. The dose-range effect of the treatment was also investigated. METHODS:
Polymer membrane capsules (1.0 cm in length and 1.0 mm in diameter) were loaded with mammalian cells that were genetically engineered to secrete CNTF. The cell-containing capsules were then surgically implanted into the vitreous of one eye of rcd1 dogs at 7 weeks of age, when retinal degeneration is in progress but not complete. The contralateral eyes were not treated. The capsules remained in the eyes for 7 weeks. At the end of the studies, the capsules were explanted, and CNTF output and cell viability were evaluated. The eyes were processed for histologic evaluation. RESULTS: In each animal, the number of rows of photoreceptor nuclei in the outer nuclear layer (ONL) was significantly higher in the eye that received a CNTF-secreting implant than in the untreated contralateral eye. No adverse effects were observed on the retina in the treated eyes. The explanted capsules produced a low level of CNTF. The cells in the capsules remained viable and densely distributed throughout. CONCLUSIONS:
CNTF delivered through encapsulated cells directly into the vitreous of the eye protects photoreceptors in the PDE6B-deficient rcd1 canine model. Furthermore, sparing of photoreceptors appeared dose-dependent with minimum protection observed at CNTF doses of 0.2 to 1.0 ng/d. Incrementally greater protection was achieved at higher doses. The surgically implanted, cell-containing capsules were well tolerated, and the cells within the capsule remained viable for the 7-week implantation interval. These results suggest that encapsulated cell therapy may provide a safe and effective strategy for treating retinal disorders in humans.
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Authors | Weng Tao, Rong Wen, Moses B Goddard, Sandy D Sherman, Pam J O'Rourke, Paul F Stabila, William J Bell, Brenda J Dean, Konrad A Kauper, Veronica A Budz, William G Tsiaras, Gregory M Acland, Sue Pearce-Kelling, Alan M Laties, Gustavo D Aguirre |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 43
Issue 10
Pg. 3292-8
(Oct 2002)
ISSN: 0146-0404 [Print] United States |
PMID | 12356837
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Ciliary Neurotrophic Factor
- Delayed-Action Preparations
- Neuroprotective Agents
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Topics |
- Animals
- Animals, Genetically Modified
- Cell Line
- Ciliary Neurotrophic Factor
(administration & dosage, pharmacology)
- Delayed-Action Preparations
- Dogs
- Dose-Response Relationship, Drug
- Drug Delivery Systems
- Equipment Design
- Humans
- Nerve Degeneration
(pathology, physiopathology)
- Neuroprotective Agents
(administration & dosage, pharmacology)
- Photoreceptor Cells
(drug effects, physiopathology)
- Rats
- Retinitis Pigmentosa
(pathology, physiopathology)
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