Postnatal weight gain modifies severity and functional outcome of oxygen-induced proliferative retinopathy.
In clinical studies, postnatal weight gain is strongly associated with retinopathy of prematurity (ROP). However, animal studies are needed to investigate the pathophysiological mechanisms of how postnatal weight gain affects the severity of ROP. In the present study, we identify nutritional supply as one potent parameter that affects the extent of retinopathy in mice with identical birth weights and the same genetic background. Wild-type pups with poor postnatal nutrition and poor weight gain (PWG) exhibit a remarkably prolonged phase of retinopathy compared to medium weight gain or extensive weight gain pups. A high (r(2) = 0.83) parabolic association between postnatal weight gain and oxygen-induced retinopathy severity is observed, as is a significantly prolonged phase of proliferative retinopathy in PWG pups (20 days) compared with extensive weight gain pups (6 days). The extended retinopathy is concomitant with prolonged overexpression of retinal vascular endothelial growth factor in PWG pups. Importantly, PWG pups show low serum levels of nonfasting glucose, insulin, and insulin-like growth factor-1 as well as high levels of ghrelin in the early postoxygen-induced retinopathy phase, a combination indicative of poor metabolic supply. These differences translate into visual deficits in adult PWG mice, as demonstrated by impaired bipolar and proximal neuronal function. Together, these results provide evidence for a pathophysiological correlation between poor postnatal nutritional supply, slow weight gain, prolonged retinal vascular endothelial growth factor overexpression, protracted retinopathy, and reduced final visual outcome.
Department of Ophthalmology, Harvard Medical School, Children’s Hospital Boston, Boston, Massachusetts 02115, USA.
Andreas
A
Stahl
Jing
J
Chen
Przemyslaw
P
Sapieha
Molly R
MR
Seaward
Nathan M
NM
Krah
Roberta J
RJ
Dennison
Tara
T
Favazza
Felicitas
F
Bucher
Chatarina
C
Löfqvist
Huy
H
Ong
Ann
A
Hellström
Sylvain
S
Chemtob
James D
JD
Akula
Lois E H
LE
Smith
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000009:adverse effects*; D010102:Oxygen Inhalation Therapy / Q000009:adverse effects; D036801:Parturition / Q000502:physiology; D011379:Prognosis; D012160:Retina / Q000378:metabolism; D012178:Retinopathy of Prematurity / Q000175:diagnosis* / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D015430:Weight Gain / Q000502:physiology*
D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen