The Nerve Growth Factor Signaling and Its Potential as Therapeutic Target for Glaucoma

Abstract

Neuroprotective therapies which focus on factors leading to retinal ganglion cells (RGCs) degeneration have been drawing more and more attention. The beneficial effects of nerve growth factor (NGF) on the glaucoma have been recently suggested, but its effects on eye tissue are complex and controversial in various studies. Recent clinical trials of systemically and topically administrated NGF demonstrate that NGF is effective in treating several ocular diseases, including glaucoma. NGF has two receptors named high affinity NGF tyrosine kinase receptor TrkA and low affinity receptor p75NTR. Both receptors exist in cells in retina like RGC (expressing TrkA) and glia cells (expressing p75NTR). NGF functions by binding to TrkA or p75NTR alone or both together. The binding of NGF to TrkA alone in RGC promotes RGC's survival and proliferation through activation of TrkA and several prosurvival pathways. In contrast, the binding of NGF to p75NTR leads to apoptosis although it also promotes survival in some cases. Binding of NGF to both TrkA and p75NTR at the same time leads to survival in which p75NTR functions as a TrkA helping receptor. This review discusses the current understanding of the NGF signaling in retina and the therapeutic implications in the treatment of glaucoma.

Neuroprotection for glaucoma: Requirements for clinical translation

“…A successful treatment regimen could target more than one of these pathways. One group of potential targets include neurotrophic factors such as NGF (Bai et al, 2010; Wang et al, 2014), BDNF (Mansour-Robaey et al, 1994; Martin et al, 2003), or CNTF (Ji et al, 2004) as pro-survival agents. Axon damage-induced apoptosis can be blocked with a variety of caspase inhibitors (Uchibayashi et al, 2011).…”

Production of functional human nerve growth factor from the saliva of transgenic mice by using salivary glands as bioreactors

“…Nerve growth factor (NGF) is a therapeutically important protein that was first identified by Cohen and Levi-Montalcini2425. It not only is clinically relevant for the treatment of various neuronal ailments such as glaucoma and Alzheimer’s disease but also has promising therapeutic potential for some non-neuronal disorders such as vascular and immune diseases2627282930. Commercial mouse NGF (mNGF) that is purified from mouse submandibular glands has been approved in China for the treatment of some nerve damage and degeneration diseases, including optic nerve injury, spinal cord injury, traumatic brain injury, Alzheimer’s disease, Parkinson’s disease, hypoxic-ischemic encephalopathy and pediatric cerebral palsy in humans.…”

Role of BDNF/TrkB pathway in the visual system: therapeutic implications for glaucoma

“…Many informative reviews have been published on mechanisms contributing to RGC apoptosis in glaucoma including mitochondrial dysfunction [15] and oxidative stress [16], endoplasmic reticulum (ER) stress and the unfolded protein response [17], neurotrophin deficits [11,18,19], excitotoxicity [20], ischemia [21], inflammation and glial activation [22,23]. Each of these pathways is a potential therapeutic target; however, our group has a keen interest in the role of brain derived neurotrophic factor (BDNF) and its cognate receptor tropomyosin-related kinase B (TrkB) in glaucoma.…”