Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats

HL Winton; RD Lund; P Adamson; Y Sauve; DJ Keegan; SV Girman; S Wang; N Kanuga; ASL Kwan; L Beauchene; A Zerbib; L Hetherington; PO Couraud; P Coffey; J Greenwood

doi:10.1073/pnas.171266298

Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats

HL Winton, RD Lund, P Adamson, Y Sauve, DJ Keegan, SV Girman, S Wang, N Kanuga, ASL Kwan, L Beauchene, A Zerbib, L Hetherington, PO Couraud, P Coffey, J Greenwood

Research output: Contribution to journal › Article (Academic Journal) › peer-review

169 Citations (Scopus)

Abstract

Royal College of Surgeons rats are genetically predisposed to undergo significant visual loss caused by a primary dysfunction of retinal pigment epithelial (RPE) cells. By using this model, we have examined the efficacy of subretinal transplantation of two independent human RIPE cell lines each exhibiting genetic modifications that confer long-term stability in vitro. The two cell lines, a spontaneously derived cell line (ARPE19) and an extensively characterized genetically engineered human RIPE cell line (h1RPE7), which expresses SV40 large T (tumor) antigen, were evaluated separately. Both lines result in a significant preservation of visual function as assessed by either behavioral or physiological techniques. This attenuation of visual loss correlates with photoreceptor survival and the presence of donor cells in the areas of rescued photoreceptors at 5 months postgrafting (6 months of age). These results demonstrate the potential of genetically modified human RPE cells for ultimate application in therapeutic transplantation strategies for retinal degenerative diseases caused by RIPE dysfunction.

Translated title of the contribution	Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats
Original language	English
Pages (from-to)	9942 - 9947
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	98
Issue number	17
DOIs	https://doi.org/10.1073/pnas.171266298
Publication status	Published - 14 Aug 2001

Keywords

Retinal Pigment Epithelium
RCS Rat
Macular Degeneration
Superior colliculus
grafts
rescue

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Winton, HL., Lund, RD., Adamson, P., Sauve, Y., Keegan, DJ., Girman, SV., Wang, S., Kanuga, N., Kwan, ASL., Beauchene, L., Zerbib, A., Hetherington, L., Couraud, PO., Coffey, P., & Greenwood, J. (2001). Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats. Proceedings of the National Academy of Sciences of the United States of America, 98(17), 9942 - 9947. https://doi.org/10.1073/pnas.171266298

Winton, HL ; Lund, RD ; Adamson, P ; Sauve, Y ; Keegan, DJ ; Girman, SV ; Wang, S ; Kanuga, N ; Kwan, ASL ; Beauchene, L ; Zerbib, A ; Hetherington, L ; Couraud, PO ; Coffey, P ; Greenwood, J. / Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 17. pp. 9942 - 9947.

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title = "Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats",

abstract = " Royal College of Surgeons rats are genetically predisposed to undergo significant visual loss caused by a primary dysfunction of retinal pigment epithelial (RPE) cells. By using this model, we have examined the efficacy of subretinal transplantation of two independent human RIPE cell lines each exhibiting genetic modifications that confer long-term stability in vitro. The two cell lines, a spontaneously derived cell line (ARPE19) and an extensively characterized genetically engineered human RIPE cell line (h1RPE7), which expresses SV40 large T (tumor) antigen, were evaluated separately. Both lines result in a significant preservation of visual function as assessed by either behavioral or physiological techniques. This attenuation of visual loss correlates with photoreceptor survival and the presence of donor cells in the areas of rescued photoreceptors at 5 months postgrafting (6 months of age). These results demonstrate the potential of genetically modified human RPE cells for ultimate application in therapeutic transplantation strategies for retinal degenerative diseases caused by RIPE dysfunction. ",

keywords = "Retinal Pigment Epithelium, RCS Rat, Macular Degeneration, Superior colliculus, grafts, rescue",

author = "HL Winton and RD Lund and P Adamson and Y Sauve and DJ Keegan and SV Girman and S Wang and N Kanuga and ASL Kwan and L Beauchene and A Zerbib and L Hetherington and PO Couraud and P Coffey and J Greenwood",

year = "2001",

month = aug,

day = "14",

doi = "10.1073/pnas.171266298",

language = "English",

volume = "98",

pages = "9942 -- 9947",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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Winton, HL, Lund, RD, Adamson, P, Sauve, Y, Keegan, DJ, Girman, SV, Wang, S, Kanuga, N, Kwan, ASL, Beauchene, L, Zerbib, A, Hetherington, L, Couraud, PO, Coffey, P & Greenwood, J 2001, 'Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats', Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 17, pp. 9942 - 9947. https://doi.org/10.1073/pnas.171266298

Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats. / Winton, HL; Lund, RD; Adamson, P; Sauve, Y; Keegan, DJ; Girman, SV; Wang, S; Kanuga, N; Kwan, ASL; Beauchene, L; Zerbib, A; Hetherington, L; Couraud, PO; Coffey, P; Greenwood, J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 17, 14.08.2001, p. 9942 - 9947.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats

AU - Winton, HL

AU - Lund, RD

AU - Adamson, P

AU - Sauve, Y

AU - Keegan, DJ

AU - Girman, SV

AU - Wang, S

AU - Kanuga, N

AU - Kwan, ASL

AU - Beauchene, L

AU - Zerbib, A

AU - Hetherington, L

AU - Couraud, PO

AU - Coffey, P

AU - Greenwood, J

PY - 2001/8/14

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N2 - Royal College of Surgeons rats are genetically predisposed to undergo significant visual loss caused by a primary dysfunction of retinal pigment epithelial (RPE) cells. By using this model, we have examined the efficacy of subretinal transplantation of two independent human RIPE cell lines each exhibiting genetic modifications that confer long-term stability in vitro. The two cell lines, a spontaneously derived cell line (ARPE19) and an extensively characterized genetically engineered human RIPE cell line (h1RPE7), which expresses SV40 large T (tumor) antigen, were evaluated separately. Both lines result in a significant preservation of visual function as assessed by either behavioral or physiological techniques. This attenuation of visual loss correlates with photoreceptor survival and the presence of donor cells in the areas of rescued photoreceptors at 5 months postgrafting (6 months of age). These results demonstrate the potential of genetically modified human RPE cells for ultimate application in therapeutic transplantation strategies for retinal degenerative diseases caused by RIPE dysfunction.

AB - Royal College of Surgeons rats are genetically predisposed to undergo significant visual loss caused by a primary dysfunction of retinal pigment epithelial (RPE) cells. By using this model, we have examined the efficacy of subretinal transplantation of two independent human RIPE cell lines each exhibiting genetic modifications that confer long-term stability in vitro. The two cell lines, a spontaneously derived cell line (ARPE19) and an extensively characterized genetically engineered human RIPE cell line (h1RPE7), which expresses SV40 large T (tumor) antigen, were evaluated separately. Both lines result in a significant preservation of visual function as assessed by either behavioral or physiological techniques. This attenuation of visual loss correlates with photoreceptor survival and the presence of donor cells in the areas of rescued photoreceptors at 5 months postgrafting (6 months of age). These results demonstrate the potential of genetically modified human RPE cells for ultimate application in therapeutic transplantation strategies for retinal degenerative diseases caused by RIPE dysfunction.

KW - Retinal Pigment Epithelium

KW - RCS Rat

KW - Macular Degeneration

KW - Superior colliculus

KW - grafts

KW - rescue

U2 - 10.1073/pnas.171266298

DO - 10.1073/pnas.171266298

M3 - Article (Academic Journal)

VL - 98

SP - 9942

EP - 9947

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 17

ER -