Mouse model of subretinal neovascularization with choroidal anastomosis.
OBJECTIVE
To characterize the phenotype and report a reliable genetic model of retinal angiogenesis and subretinal neovascularization in the mouse.


METHODS
The mouse phenotype was characterized using ophthalmoscopy, fundus photography, fluorescein angiography, electroretinography, histology, gene sequencing, and linkage analysis.


RESULTS
Scattered pink-gray retinal lesions were found on ophthalmoscopy and were confirmed to be subretinal neovascularization on fluorescein angiography. On histologic examination, outer plexiform retinal neovascularization with growth into the subretinal space was found as early as postnatal Day 15. On genetic analysis, homozygosity of the Vldlr mutation always segregated with the retinal angiogenesis, whereas normal and heterozygous mice had no neovascularization. The histologic studies 15 to 18 days consistently showed new outer plexiform neovascular vessels drawn to the subretinal space by 20 days, and by 30 to 50 days, subretinal hemorrhages and choroidal anastomoses were common. Mice by 8 months had increased vascularity of the iris and ciliary body.


CONCLUSIONS
The Vldlr mutation in the mouse provides a good model for retinal angiogenesis and subretinal neovascularization. Finding a strong association between retinal angiogenesis and a very low density lipid receptor mutation is new, and study of lipid receptor physiology may broaden the understanding of retinal angiogenesis.
Heckenlively
John R
JR
Jules Stein Eye Institute, UCLA School of Medicine, University of California at Los Angeles, 100 Stein Plaza, Los Angeles, CA 90095, USA. heckenlively@jsei.ucla.edu
Hawes
Norman L
NL
Friedlander
Martin
M
Nusinowitz
Steven
S
Hurd
Ronald
R
Davisson
Muriel
M
Chang
Bo
B
D000818:Animals; D001164:Arteriovenous Fistula / Q000235:genetics* / Q000473:pathology; D002829:Choroid / Q000098:blood supply*; D020256:Choroidal Neovascularization / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D010781:Photography; D011973:Receptors, LDL / Q000235:genetics*; D015861:Retinal Neovascularization / Q000235:genetics* / Q000473:pathology; D012171:Retinal Vessels / Q000002:abnormalities*
D011973:Receptors, LDL; C036053:VLDL receptor