TY - JOUR
T1 - Early postnatal hyperoxia in mice leads to severe persistent vitreoretinopathy
AU - McMenamin, Paul G.
AU - Kenny, Rachel
AU - Tahija, Sjakon
AU - Lim, Jeremiah
AU - Naranjo Golborne, Cecilia
AU - Chen, Xiangting
AU - Bouch, Sheena
AU - Sozo, Foula
AU - Bui, Bang
PY - 2016/12/1
Y1 - 2016/12/1
N2 - PURPOSE. To describe a mouse model of hyperoxia-induced vitreoretinopathy that replicated some of the clinical and pathologic features encountered in infants with severe retinopathy of prematurity and congenital ocular conditions such as persistent hyperplastic primary vitreous. METHODS. Experimental mice (C57BL/6J) were exposed to 65% oxygen between postnatal days (P)0 to P7 and studied at P10, P14, and 3, 5, 8, 20, and 40 weeks. Controls were exposed to normoxic conditions. Fundus imaging and fluorescein angiography were performed at all time points, and spectral-domain optical coherence tomography (SD-OCT) and electroretinography were performed at 8-and 20-week time points. Eyes were processed for resin histology, frozen sections, and retinal whole mounts. Immunostaining was performed to visualize vasculature isolectin B4 (Ib4), collagen type IV, glial fibrillary acidic protein, and α-smooth muscle actin. RESULTS. Early exposure to hyperoxia resulted in bilateral vitreous hemorrhages at 3 weeks. From 5 weeks onward there were extensive zones of retinal degeneration, scarring or gliosis, retinal folding, and detachments caused by traction of α-smooth muscle actin-positive vitreous membranes. Tortuous retinal vessels, together with hyperplastic and persistence of hyaloid vessels are evident into adulthood. In the early stages (P10-3 weeks), branches from the tunica vasculosa lentis (TVL) supplied the marginal retina until retinal vessels were established. The peripheral retina remained poorly vascularized into adulthood. Electroretinography revealed 50% to 60% diminution in retinal function in adult mice that strongly correlated with vitreal changes identified using SD-OCT. CONCLUSIONS. This animal model displays a mixture of vitreoretinal pathologic changes that persist into adulthood. The model may prove valuable in experimental investigations of therapeutic approaches to blinding conditions caused by vitreous and retinal abnormalities.
AB - PURPOSE. To describe a mouse model of hyperoxia-induced vitreoretinopathy that replicated some of the clinical and pathologic features encountered in infants with severe retinopathy of prematurity and congenital ocular conditions such as persistent hyperplastic primary vitreous. METHODS. Experimental mice (C57BL/6J) were exposed to 65% oxygen between postnatal days (P)0 to P7 and studied at P10, P14, and 3, 5, 8, 20, and 40 weeks. Controls were exposed to normoxic conditions. Fundus imaging and fluorescein angiography were performed at all time points, and spectral-domain optical coherence tomography (SD-OCT) and electroretinography were performed at 8-and 20-week time points. Eyes were processed for resin histology, frozen sections, and retinal whole mounts. Immunostaining was performed to visualize vasculature isolectin B4 (Ib4), collagen type IV, glial fibrillary acidic protein, and α-smooth muscle actin. RESULTS. Early exposure to hyperoxia resulted in bilateral vitreous hemorrhages at 3 weeks. From 5 weeks onward there were extensive zones of retinal degeneration, scarring or gliosis, retinal folding, and detachments caused by traction of α-smooth muscle actin-positive vitreous membranes. Tortuous retinal vessels, together with hyperplastic and persistence of hyaloid vessels are evident into adulthood. In the early stages (P10-3 weeks), branches from the tunica vasculosa lentis (TVL) supplied the marginal retina until retinal vessels were established. The peripheral retina remained poorly vascularized into adulthood. Electroretinography revealed 50% to 60% diminution in retinal function in adult mice that strongly correlated with vitreal changes identified using SD-OCT. CONCLUSIONS. This animal model displays a mixture of vitreoretinal pathologic changes that persist into adulthood. The model may prove valuable in experimental investigations of therapeutic approaches to blinding conditions caused by vitreous and retinal abnormalities.
KW - Disease model
KW - Hyaloid vasculature
KW - Hyperoxia
KW - Retinal vessels
KW - Vitreoretinopathy
UR - http://www.scopus.com/inward/record.url?scp=85003604993&partnerID=8YFLogxK
U2 - 10.1167/iovs.16-19928
DO - 10.1167/iovs.16-19928
M3 - Article
AN - SCOPUS:85003604993
SN - 1552-5783
VL - 57
SP - 6513
EP - 6526
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 15
ER -