Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)3292-3298
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume43
Issue number10
StatePublished - Oct 1 2002
Externally publishedYes

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Ciliary Neurotrophic Factor
Retinitis Pigmentosa
Capsules
Animal Models
Canidae
Retinal Degeneration
Cell- and Tissue-Based Therapy
Retina
Cell Survival
Polymers
Dogs

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Tao, W., Wen, R., Goddard, M. B., Sherman, S. D., O'Rourke, P. J., Stabila, P. F., ... Aguirre, G. D. (2002). Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa. Investigative Ophthalmology and Visual Science, 43(10), 3292-3298.

Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa. / Tao, Weng; Wen, Rong; Goddard, Moses B.; Sherman, Sandy D.; O'Rourke, Pam J.; Stabila, Paul F.; Bell, William J.; Dean, Brenda J.; Kauper, Konrad A.; Budz, Veronica A.; Tsiaras, William G.; Acland, Gregory M.; Pearce-Kelling, Sue; Laties, Alan M.; Aguirre, Gustavo D.

In: Investigative Ophthalmology and Visual Science, Vol. 43, No. 10, 01.10.2002, p. 3292-3298.

Research output: Contribution to journalArticle

Tao, W, Wen, R, Goddard, MB, Sherman, SD, O'Rourke, PJ, Stabila, PF, Bell, WJ, Dean, BJ, Kauper, KA, Budz, VA, Tsiaras, WG, Acland, GM, Pearce-Kelling, S, Laties, AM & Aguirre, GD 2002, 'Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa', Investigative Ophthalmology and Visual Science, vol. 43, no. 10, pp. 3292-3298.
Tao, Weng ; Wen, Rong ; Goddard, Moses B. ; Sherman, Sandy D. ; O'Rourke, Pam J. ; Stabila, Paul F. ; Bell, William J. ; Dean, Brenda J. ; Kauper, Konrad A. ; Budz, Veronica A. ; Tsiaras, William G. ; Acland, Gregory M. ; Pearce-Kelling, Sue ; Laties, Alan M. ; Aguirre, Gustavo D. / Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa. In: Investigative Ophthalmology and Visual Science. 2002 ; Vol. 43, No. 10. pp. 3292-3298.
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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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T1 - Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa

AU - Tao, Weng

AU - Wen, Rong

AU - Goddard, Moses B.

AU - Sherman, Sandy D.

AU - O'Rourke, Pam J.

AU - Stabila, Paul F.

AU - Bell, William J.

AU - Dean, Brenda J.

AU - Kauper, Konrad A.

AU - Budz, Veronica A.

AU - Tsiaras, William G.

AU - Acland, Gregory M.

AU - Pearce-Kelling, Sue

AU - Laties, Alan M.

AU - Aguirre, Gustavo D.

PY - 2002/10/1

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N2 - 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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