BMP-4 mRNA is decreased in the retinas of mice with ischemic retinopathy

Purpose: Bone morphogenic proteins (BMPs) are members of the transforming growth factor-beta superfamily of intercellular signaling molecules- We have previously demonstrated that BMP-1 is expressed in ihe retina. This study was designed to determine if BMP-4 mRNA is altered in ischémie retinopathy. Methods: Ischémie retinopathy wis induced by exposing postnatal day 7 (P7) C57BL/6J mice to 75% oxygen for 5 days followed by return lo room air for 5 days. Mice with ischémie retinopathy and controls were sacrificed on P17, eyes were enucleated, and in situ hybridization was done on retinal frozen sections using digoxygenin-labeled anti-sense an-1 sense BMP-4 riboprobes. Images were digitized and densitometry was done ising Image Pro Plus 2 software. Results: As noted previously, control P17 mice showed promineni differential staining with anti-sense probe in the outer nuclear iayer (ONL), inner nuclear layer (INL) and ganglion cell layer. Mice with ischémie retinopathy showed a striking decrease in BMP-4 mRNA in all retinal layers. Mean (n-4) optical density units for anti-sense staining minus background for control versus ischémie retinopathy was 35.61 8.4 versus 4.6 ±6.3 (p=0.0042) in ONL and 40.1 ±18.8 versus 3.2 ± 4.3 (p=0.02) in INL. Conclusions: BMP-4 mRNA is markedly decreased in the retinas' of mice with ischémie retinopathy. This raises the possibility thai alterations in BMP-4 levels could play a role in the pathophysiology of retinal neovascularization in ischémie retinopathy.