Overexpression of the X-Linked Inhibitor of Apoptosis Protects Against Retinal Degeneration in a Feline Model of Retinal Detachment.
Retinal detachment is an acute disorder in humans that is caused by trauma or disease, and it can often lead to permanent visual deficits that result from the death of photoreceptors in the retina. The final pathway for photoreceptor cell death is apoptosis and necroptosis. The X-linked inhibitor of apoptosis (XIAP) has been shown to block both of these cell death pathways. This study tested the effects of XIAP on photoreceptor survival in a feline model of retinal detachment. The study was performed in 12 cats, divided into two experimental groups. Six animals received a subretinal injection of adeno-associated virus (AAV) carrying XIAP, and six animals received AAV carrying green fluorescent protein (GFP) as a control. Three weeks after viral delivery, retinas were detached by injecting C3F8gas into the subretinal space. Optical coherence tomography revealed that the retinal detachments resolved within 3-6 weeks as the gas was slowly resorbed. Analysis of histological sections through the plane of the detachment showed significant preservation of the photoreceptor layer in AAV-XIAP-treated animals compared to AAV-GFP-treated animals at 9 weeks after the detachment. XIAP-treated detached retinas were similar to intact controls. These studies support the potential for XIAP therapy in the treatment of human retinal detachment.
1 Department of Cellular and Molecular Medicine, University of Ottawa , Ottawa, Canada .
Sarah J
SJ
Wassmer
2 Department of Ophthalmology, University of Ottawa , Ottawa, Canada .|3 Ottawa Hospital Research Institute , Regenerative Medicine, Ottawa, Canada .|4 Ottawa Hospital, Eye Institute , Ottawa, Canada .
Brian C
BC
Leonard
1 Department of Cellular and Molecular Medicine, University of Ottawa , Ottawa, Canada .|2 Department of Ophthalmology, University of Ottawa , Ottawa, Canada .|3 Ottawa Hospital Research Institute , Regenerative Medicine, Ottawa, Canada .|4 Ottawa Hospital, Eye Institute , Ottawa, Canada .
Stuart G
SG
Coupland
3 Ottawa Hospital Research Institute , Regenerative Medicine, Ottawa, Canada .
Adam N
AN
Baker
4 Ottawa Hospital, Eye Institute , Ottawa, Canada .
John
J
Hamilton
5 Department of Ophthalmology, University of Florida College of Medicine , Gainesville, Florida.
William W
WW
Hauswirth
1 Department of Cellular and Molecular Medicine, University of Ottawa , Ottawa, Canada .|2 Department of Ophthalmology, University of Ottawa , Ottawa, Canada .|3 Ottawa Hospital Research Institute , Regenerative Medicine, Ottawa, Canada .|4 Ottawa Hospital, Eye Institute , Ottawa, Canada .
Catherine
C
Tsilfidis
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002415:Cats; D002460:Cell Line; D000229:Dependovirus / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005466:Fluorocarbons / Q000008:administration & dosage; D015870:Gene Expression; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056965:Injections, Intraocular; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D012163:Retinal Detachment / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015398:Signal Transduction; D041623:Tomography, Optical Coherence; D019076:Transgenes; D016896:Treatment Outcome; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics* / Q000378:metabolism
D005466:Fluorocarbons; D051636:X-Linked Inhibitor of Apoptosis Protein; D049452:Green Fluorescent Proteins; C042852:perflutren
XIAP; adeno-associated virus; apoptosis; gene therapy; retinal detachment