Human cone photoreceptor transplantation stimulates retinal remodelling and restores retinal and visual function in AIPL1 mouse model of end-stage Leber Congenital Amaurosis

Christopher Procyk; Anna Melati; Joana Ribeiro; Jingshu Liu; Matthew Branch; Menahil Tariq; Aikaterini Kalargyrou; Majid Moshtagh Khorasani; Emma West; Sander Smith; Anai Gonzalez-Cordero; Robin Ali; Rachael Pearson

Human cone photoreceptor transplantation stimulates retinal remodelling and restores retinal and visual function in AIPL1 mouse model of end-stage Leber Congenital Amaurosis

Christopher Procyk, Anna Melati, Joana Ribeiro, Jingshu Liu, Matthew Branch, Menahil Tariq, Aikaterini Kalargyrou, Majid Moshtagh Khorasani, Emma West, Sander Smith, Anai Gonzalez-Cordero, Robin Ali, Rachael Pearson

Gene Therapy and Regenerative Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Photoreceptor degeneration is a leading cause of untreatable sight-loss. Previously, we showed that human pluripotent stem cell-derived cone photoreceptors (human cones) can rescue retinal function in the Rd1 mouse model of rod-cone dystrophy. However, retinal degenerations display markedly different severities and concomitant remodelling of the remaining retina; for photoreceptor replacement therapy to be broadly effective, it must work for a variety of disease phenotypes. Here, we sought to rescue the Aipl1-/- model of Leber Congenital Amaurosis, a particularly fast, severe condition. After transplantation of human cones, host cone bipolar cells underwent extensive remodelling and formed nascent synaptic-like connections. Electrophysiological recordings showed robust rescue of light-evoked activity across visually relevant photopic intensities and treated mice exhibited visually-evoked optokinetic head tracking behaviour. Thus, human cone photoreceptor replacement therapy is feasible even in very severe cases of retinal dystrophy, offering promise as a disease-agnostic therapy in LCA and in other advanced retinal degenerations.

Original language	English
Journal	Stem Cell Reports
Publication status	Accepted/In press - 19 Feb 2025

Cite this

Procyk, C., Melati, A., Ribeiro, J., Liu, J., Branch, M., Tariq, M., Kalargyrou, A., Moshtagh Khorasani, M., West, E., Smith, S., Gonzalez-Cordero, A., Ali, R., & Pearson, R. (Accepted/In press). Human cone photoreceptor transplantation stimulates retinal remodelling and restores retinal and visual function in AIPL1 mouse model of end-stage Leber Congenital Amaurosis. Stem Cell Reports.

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title = "Human cone photoreceptor transplantation stimulates retinal remodelling and restores retinal and visual function in AIPL1 mouse model of end-stage Leber Congenital Amaurosis",

abstract = "Photoreceptor degeneration is a leading cause of untreatable sight-loss. Previously, we showed that human pluripotent stem cell-derived cone photoreceptors (human cones) can rescue retinal function in the Rd1 mouse model of rod-cone dystrophy. However, retinal degenerations display markedly different severities and concomitant remodelling of the remaining retina; for photoreceptor replacement therapy to be broadly effective, it must work for a variety of disease phenotypes. Here, we sought to rescue the Aipl1-/- model of Leber Congenital Amaurosis, a particularly fast, severe condition. After transplantation of human cones, host cone bipolar cells underwent extensive remodelling and formed nascent synaptic-like connections. Electrophysiological recordings showed robust rescue of light-evoked activity across visually relevant photopic intensities and treated mice exhibited visually-evoked optokinetic head tracking behaviour. Thus, human cone photoreceptor replacement therapy is feasible even in very severe cases of retinal dystrophy, offering promise as a disease-agnostic therapy in LCA and in other advanced retinal degenerations. ",

author = "Christopher Procyk and Anna Melati and Joana Ribeiro and Jingshu Liu and Matthew Branch and Menahil Tariq and Aikaterini Kalargyrou and {Moshtagh Khorasani}, Majid and Emma West and Sander Smith and Anai Gonzalez-Cordero and Robin Ali and Rachael Pearson",

year = "2025",

month = feb,

day = "19",

language = "English",

journal = "Stem Cell Reports",

issn = "2213-6711",

publisher = "CELL PRESS",

}

TY - JOUR

T1 - Human cone photoreceptor transplantation stimulates retinal remodelling and restores retinal and visual function in AIPL1 mouse model of end-stage Leber Congenital Amaurosis

AU - Procyk, Christopher

AU - Melati, Anna

AU - Ribeiro, Joana

AU - Liu, Jingshu

AU - Branch, Matthew

AU - Tariq, Menahil

AU - Kalargyrou, Aikaterini

AU - Moshtagh Khorasani, Majid

AU - West, Emma

AU - Smith, Sander

AU - Gonzalez-Cordero, Anai

AU - Ali, Robin

AU - Pearson, Rachael

PY - 2025/2/19

Y1 - 2025/2/19

N2 - Photoreceptor degeneration is a leading cause of untreatable sight-loss. Previously, we showed that human pluripotent stem cell-derived cone photoreceptors (human cones) can rescue retinal function in the Rd1 mouse model of rod-cone dystrophy. However, retinal degenerations display markedly different severities and concomitant remodelling of the remaining retina; for photoreceptor replacement therapy to be broadly effective, it must work for a variety of disease phenotypes. Here, we sought to rescue the Aipl1-/- model of Leber Congenital Amaurosis, a particularly fast, severe condition. After transplantation of human cones, host cone bipolar cells underwent extensive remodelling and formed nascent synaptic-like connections. Electrophysiological recordings showed robust rescue of light-evoked activity across visually relevant photopic intensities and treated mice exhibited visually-evoked optokinetic head tracking behaviour. Thus, human cone photoreceptor replacement therapy is feasible even in very severe cases of retinal dystrophy, offering promise as a disease-agnostic therapy in LCA and in other advanced retinal degenerations.

AB - Photoreceptor degeneration is a leading cause of untreatable sight-loss. Previously, we showed that human pluripotent stem cell-derived cone photoreceptors (human cones) can rescue retinal function in the Rd1 mouse model of rod-cone dystrophy. However, retinal degenerations display markedly different severities and concomitant remodelling of the remaining retina; for photoreceptor replacement therapy to be broadly effective, it must work for a variety of disease phenotypes. Here, we sought to rescue the Aipl1-/- model of Leber Congenital Amaurosis, a particularly fast, severe condition. After transplantation of human cones, host cone bipolar cells underwent extensive remodelling and formed nascent synaptic-like connections. Electrophysiological recordings showed robust rescue of light-evoked activity across visually relevant photopic intensities and treated mice exhibited visually-evoked optokinetic head tracking behaviour. Thus, human cone photoreceptor replacement therapy is feasible even in very severe cases of retinal dystrophy, offering promise as a disease-agnostic therapy in LCA and in other advanced retinal degenerations.

M3 - Article

SN - 2213-6711

JO - Stem Cell Reports

JF - Stem Cell Reports

ER -

Human cone photoreceptor transplantation stimulates retinal remodelling and restores retinal and visual function in AIPL1 mouse model of end-stage Leber Congenital Amaurosis

Abstract

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