Nerve Growth Factor Modulation of Retinal Ganglion Cell Physiology

Abstract

Nerve growth factor (NGF) is an endogenous neurotrophin involved in the development, maintenance and regeneration of mammalian sympathetic and sensory neurons. Additionally, NGF is known to have trophic and differentiating activity on several populations of cholinergic neurons of the central nervous system (CNS), and to act as a differentiation factor in the development of the visual cortex. The paramount functions of NGF in the visual system are also highlighted by the presence of this neurotrophin and both its receptors TrkA and p75 in most intra-ocular tissues, including lens, vitreous, choroid, iris, and trabecular meshwork. In the retina, NGF is produced and utilized specifically by retinal ganglion cells (RGC), bipolar neurons and glial cells, and is thought to have crucial protective effects in several disease states. Studies on the role of NGF on RGCs survival following optic nerve transection, ischemic injury, ocular hypertension and glaucoma are discussed in this review.

Potential of Müller Glia for Retina Neuroprotection

“…It signals with high affinity through the TrkA receptor and plays a pivotal role during the development, maintenance, and regeneration of sensory neurons in the CNS. 45 It is highly expressed in the human eye during development and its mature form selectively binds to TrkA, promoting neural cell survival within the retina, in particular of retinal ganglion cells (RGCs). 46 In addition to its neurotrophic functions on retinal neurons, NGF has been shown to be a potent antioxidant, as demonstrated by its effect in preventing oxidant-induced lipid peroxide production by Müller glia in response to H 2 O 2 -induced oxidative stress.…”

Dynamic Nature of the p75 Neurotrophin Receptor in Response to Injury and Disease

“…However, its interaction with p75 NTR has received a great deal of attention due to two important discoveries; 1) p75 NTR -sortilin heterodimers activate apoptotic pathways in neurons and other cells, a process often used for cell selection during development (Hempstead, 2006; Kraemer et al, 2014) and 2) pro-neurotrophins bind with high affinity to the sortilin-p75 NTR complex and initiate cell death signaling(Lee et al, 2001) via the transcription factor JNK-3 and activation of c-Jun. The p75 NTR has been shown to be important for initiation of apoptotic cell death in developing neurons(Huang and Reichardt, 2001; Teng et al, 2005; Jansen et al, 2007; Nykjaer and Willnow, 2012), retinal neurons(Frade and Barde, 1998; Roberti et al, 2014) sympathetic neurons(Kenchappa et al, 2010) and oligodendrocytes(Beattie et al, 2002). However, while sortilin’s role in cell death has received a great deal of attention, it is important to note that it is one of many functions.…”

Exploring Serum Levels of Brain Derived Neurotrophic Factor and Nerve Growth Factor Across Glaucoma Stages

“…The first discovered neurotrophic factor, NGF is produced and utilized specifically by RGCs, bipolar neurons and glial cells, and is thought to have crucial protective effects in several disease states [11]. …”