Choroidal neovascularization in transgenic mice expressing prokineticin 1: an animal model for age-related macular degeneration.
The prognosis of choroidal neovascularization (CNV) in age-related macular degeneration (AMD) is poor and existing treatments are limited in retarding the progression of disease. The development of an animal model for AMD will be beneficial for finding potential treatments, including gene therapy. Recently prokineticin 1 (hPK1) was identified as a mitogen of fenestrated endothelium. We hypothesized that hPK1 could induce CNV, a hallmark of the exudative or wet form of AMD, since the endothelium of the choriocapillaris, but not retinal endothelium, has fenestration. We generated transgenic mice expressing hPK1 in the retina using the rhodopsin promoter. In these transgenic mice, an enlarged vascular bed of choroid resembling CNV was observed without any morphological changes in the retinal vasculature. In addition, the major fluorophore of lipofuscin, N-retinylidene-N-retinylethanolamine, which has several potential cytotoxic effects on the RPE, was accumulated approximately twice as much in the transgenic mouse eyes compared to controls. hPK1 could be one of the causative factors of AMD and the transgenic mouse exhibiting CNV may be useful to establish treatments for the wet form of AMD.
Tanaka
Nobushige
N
Laboratory of Genetics, The Salk Institute, La Jolla, CA, USA.
Ikawa
Masahito
M
Mata
Nathan L
NL
Verma
Inder M
IM
D000367:Age Factors; D000375:Aging / Q000235:genetics* / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D002829:Choroid / Q000098:blood supply* / Q000503:physiopathology; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000235:genetics*; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000235:genetics*
D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived