Nf-B Is Involved in Retinal Ganglion Cell Death After Axonal, Ischemic and High Intraocular Pressure Injuries

Abstract

Purpose: : The molecular mechanisms of retinal ganglion cell death in glaucoma are largely unknown. Nuclear factor- ΚB (NF-ΚB) is a common transcription factor which has several target genes. It plays a significant role in cell death and survival in different cell types and under several pathological circumstances. It is activated by a variety of stimuli, such as stress, ischemia/reperfusion injury, bacterial endotoxin, viral proteins, tumor necrosis factor-alpha and interleukin-1. Controversial reports exist on the role of NF-ΚB in degeneration and death of neurons. Because the function of NF-ΚB in retinal ganglion cell death remained unclear, we sought to clarify this issue.

Methods: : To study the involvement of NF-ΚB in injury-induced cell death in retina, we studied NF-ΚB expression in normal rat retina, in retinas after optic nerve transection (ONT), selective ligature of ophthalmic vessels (SLOV) and acute increase in intraocular pressure (IIOP). The animals were sacrified 3d, 7d and 14d (ONT, SLOV) and 1d, 7d and 14d (IIOP) after injury. Total RNA was extracted with Trizol, analyzed for purity and cDNA was produced. The mRNA levels were determined by using real time quantitative PCR with SYBR green assay. Untreated animals were used as controls and the expression levels were normalized against β-actin.

Results: : The relative level of NF-ΚB mRNA in retina was significantly higher 3 and 7 days after injury comparing to normal level. After 14 days mRNA level were near or below normal in all injury models, except in IIOP samples in which the level was still increased 2-fold.

Conclusions: : Our results suggest that NF-ΚB is involved in injury-induced retinal ganglion cell death and indicate that the increase in NF-ΚB expression might promote cell death after ONT, SLOV and IIOP.

Keywords: apoptosis/cell death • retina: proximal (bipolar, amacrine, and ganglion cells) • optic nerve