TMP Prevents Retinal Neovascularization and Imparts Neuroprotection in an Oxygen-Induced Retinopathy Model

Abstract

Purpose: : To evaluate the effects of Tetramethylpyrazine (TMP) on retinal pathological neovascularization and neuroprotection in an oxygen-induced retinopathy (OIR) model.

Methods: : Neonatal C57BL/6J mice were subjected to 75% oxygen from postnatal day (P) 7 to P12 and then were abruptly placed in room air. TMP (200mg/kg) or normal saline was given daily from P12, and mice were sacrificed at P14, P15 or P17. Retina whole-mount and immunofluorescence were used to assess the effects of TMP on retinal neurovascular repair.

Results: : Administration of TMP during ischemic phase of the retinopathy effectively prevented pathological intravitreal neovascular tufts (P<0.01), and decreased the avascular area of the retina (P<0.05). These morphologic changes were associated with the protective role of TMP in markedly enhancing the formation of endothelial tip cells at the edges of the repairing capillary networks and preserving the astrocytic template in the avascular area. TMP also reduced the reactive expression of GFAP in Müller cells. In the avascular area of TMP-treated retinas, there was a less obvious loss of amacrine cell bodies and disorganized distinct bands; the number of both rod bipolar and horizontal cell bodies, as well as the density of their synaptic terminals in the outer plexiform layer, was greater than in OIR control mice. Moreover, TMP decreased the loss of alignment of Müller cell bodies and distortion of processes observed in OIR control mice.

Conclusions: : TMP improved neurovascular recovery by preventing retinal pathological neovascularization, accelerating physiological revascularization, and protecting retinal astroglias and neurons from ischemia-induced cell death.

Keywords: neuroprotection • retinal neovascularization • astrocyte