Adiponectin protects against hyperglycemia-induced retinal abnormalities in retinopathy of prematurity

Abstract

Purpose : Retinopathy of prematurity (ROP) is a blinding eye disorder in premature infants. Hyperglycemia is correlated with all stages especially proliferative ROP as well as with decreased serum adiponectin (APN) levels. Adipocyte-derived APN influences glucose and lipid metabolism in many tissues and serum APN levels correlate with postnatal growth and gestational age. Full-term newborns have higher APN levels in cord blood than preterm infants. We previously showed that in preterm infants, lower serum APN levels correlate with increased ROP development. We aimed to determine if APN protects against the hyperglycemia-induced retinal abnormalities in ROP.

Methods : APN^-/- (KO) and wild-type (WT) mice were treated with streptozotocin (STZ) to induce hyperglycemia. In the mouse model of STZ-induced hyperglycemia in oxygen-induced retinopathy (STZ/OIR), at P17, blood glucose levels were recorded; retinal vaso-obliteration and neovascularization (NV) were quantified. Electroretinography was examined at P30. Ex vivo choroidal assay was conducted. Retinal notch signaling in normal and neovascular blood vessels was examined with laser-captured microdissection.

Results : In STZ/OIR, the combination of hyperglycemia and APN deficiency exacerbated retinal NV (APN^-/--STZ/WT-control=2.4; WT-STZ/WT-control=1.5; APN^-/--control/WT-control=1.5). Hyperglycemia attenuated the sensitivity of a-wave, sensitivity and amplitude of b-wave as well as the summed oscillatory potentials amplitude. Hyperglycemia inhibited ex vivo choroidal microvascular sprouting especially with APN deficiency. Reduced expression of notch 1 to 4 was observed in neovessels at P17.

Conclusions : Hyperglycemia worsens retinopathy in neonatal mice and APN deficiency exacerbates hyperglycemic retinopathy, suggesting that APN might be a potential therapeutic target for the treatment of hyperglycemia-associated retinal abnormalities.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.