NGF and NGF-receptor expression of cultured immortalized human corneal endothelial cells

Several growth factors, including nerve growth factor (NGF) and vascular endothelial growth factor (VEGF), play an important role in the homeostasis of the ocular surface. The involvement of both these growth factors in the pathophysiology of intraocular tissues has been extensively investigated. Despite the expression of NGF receptors by corneal endothelium, to date the role of NGF on the endothelial cell remains to be determined. Using a clonal cell line of human corneal endothelial cells, the aim of this study was to investigate the expression of the NGF-receptor and the potential partnership of NGF and VEGF in maintaining cell viability in vitro

Capsaicin-induced corneal sensory denervation and healing impairment are reversed by NGF treatment.

PURPOSE. We aimed to evaluate the nerve growth factor (NGF) pathway and its influence on corneal healing mechanisms in normal conditions and in an animal model of corneal denervation induced by capsaicin. METHODS. Peripheral sensory damage was induced in rat pups by subcutaneous injection of capsaicin and the effects evaluated by hot-plate test, corneal nerve count, and tear secretion. Corneal damage was induced in capsaicin-treated and -untreated rats by epithelial scraping. Healing rate; NGF pathway (NGF, tyrosine kinase A [TrkA], p75); and the stem cell marker p63 were evaluated by RT-PCR, ELISA, Western blot, and immunohistochemistry. The effects of exogenous NGF administration as eye drop formulation were also tested. RESULTS. Capsaicin treatment induced a significant reduction of peripheral sensitivity, corneal innervation, tear secretion, and corneal healing rate. The ocular effects of capsaicin treatment were associated with an NGF pathway alteration. NGF eye drop treatment aided corneal healing mechanisms through a significant increase in the NGF receptors TrkA and p75, and in the stem cell marker p63. CONCLUSIONS. In this study, we show that an alteration in the NGF pathway is responsible for a delay in corneal healing in an animal model of sensory denervation. Moreover, we show that NGF eye drop administration modulates corneal innervation, epithelial cell healing, and corneal stem cells. These findings may trigger further research on the role of the NGF pathway in limbal stem cell deficiency. (Invest Ophthalmol Vis Sci. 2012; 53:8280‐8287) DOI:10.1167/iovs.12-1059

Bevacizumab eye drop treatment stimulates tear secretion in rats through changes in VEGF and NGF lacrimal gland levels

VEGF and NGF are known to modulate corneal healing, neovascularisation and tear secretion. While a VEGF-NGF cross talk has been recently shown to modulate corneal healing in rats, it is not known whether it also plays a role in the regulation of lacrimal function. In this study we aim to investigate the effects of anti-VEGF eye drop treatment on lacrimal gland function and on the local expression of VEGF and NGF in rats. Tear function was measured in 3 months old rats by modified Schirmer test at baseline and after 3 weeks of topical anti-VEGF eye drop treatment. Whole lacrimal glands from rats were removed after treatment and analysed by ELISA for VEGF and NGF levels. To investigate if the effects of anti-VEGF were mediated by changes in the NGF-pathway, we repeated the experiments in RCS rats, a strain with NGF-pathway impairment associated with decreased tear flow. After topical treatment with anti-VEGF eye drops, an increase in tear secretion was observed in both wild-type and RCS rats. A significant decrease of VEGF levels was also observed in lacrimal glands of both RCS and SD rats, accompanied by a significant increase in NGF levels. Inhibition of VEGF at the ocular surface in rats results in changes of tear function and lacrimal gland levels of VEGF and NGF. Further studies on the VEGF/NGF cross-talk at the ocular surface may expand our knowledge on the pathogenesis of several diseases characterized by tear dysfunction

Nerve growth factor eye drops improve visual acuity and electrofunctional activity in age-related macular degeneration: a case report

Age-related macular degeneration (ARMD) is a severe disease affecting visual function in the elderly. Currently available surgical and medical options do not guarantee a significant impact on the outcome of the disease. We describe the effects of nerve growth factor eye drop treatment in a 94 years old female with ARMD, whose visual acuity was progressively worsening in spite of previous surgical and medical treatments. NGF eye drops improved visual acuity and electrofunctional parameters as early as 3 months after initiation of treatment. These results are in line with previous reports on a neuroprotective effect of NGF on retinal cells and on NGF eye drops bioavailability in the retina and optic nerve. No side effects were observed after five years of follow-up, suggesting that topical NGF treatment may be a safe and effective therapy for ARMD

Nerve growth factor in the developing and adult lacrimal glands of rat with and without inherited retinitis pigmentosa

In the present study, we investigated lacrimal function and presence of the neurotrophin nerve growth factor (NGF) and its receptors in the lacrimal gland (LG) of normal rats and rats with inherited retinitis pigmentosa (IRP)

Clinical applications of NGF in ocular diseases

Nerve Growth Factor (NGF) and its receptors TrkA and p75 are expressed in physiological states in the anterior and posterior segments of the human eye, where they exert several tissue-specific functions. The roles played by NGF in the homeostasis of the eye and in vision are, therefore, crucial and have been widely investigated both in vitro and in vivo, with growing evidence of an NGF-pathway alteration in several ocular diseases. In this review we describe the functions of NGF in health and diseases states of the eye, and discuss the potential therapeutic effectiveness of NGF in preliminary clinical reports performed in severe ocular diseases unresponsive to any standard treatment. In fact, pharmacodynamic studies showing that NGF administered topically on the ocular surface affects not only the ocular surface but is also able to reach the retina, optic nerve and brain, recently opened new perspectives for the treatment of challenging ocular surface diseases, optic nerve diseases, and degenerative diseases of the retina currently lacking an effective therapy

Capsaicin-Induced Corneal Sensory Denervation and Healing Impairment Are Reversed by NGF Treatment

PURPOSE. We aimed to evaluate the nerve growth factor (NGF) pathway and its influence on corneal healing mechanisms in normal conditions and in an animal model of corneal denervation induced by capsaicin. METHODS. Peripheral sensory damage was induced in rat pups by subcutaneous injection of capsaicin and the effects evaluated by hot-plate test, corneal nerve count, and tear secretion. Corneal damage was induced in capsaicin-treated and -untreated rats by epithelial scraping. Healing rate; NGF pathway (NGF, tyrosine kinase A [TrkA], p75); and the stem cell marker p63 were evaluated by RT-PCR, ELISA, Western blot, and immunohistochemistry. The effects of exogenous NGF administration as eye drop formulation were also tested. RESULTS. Capsaicin treatment induced a significant reduction of peripheral sensitivity, corneal innervation, tear secretion, and corneal healing rate. The ocular effects of capsaicin treatment were associated with an NGF pathway alteration. NGF eye drop treatment aided corneal healing mechanisms through a significant increase in the NGF receptors TrkA and p75, and in the stem cell marker p63. CONCLUSIONS. In this study, we show that an alteration in the NGF pathway is responsible for a delay in corneal healing in an animal model of sensory denervation. Moreover, we show that NGF eye drop administration modulates corneal innervation, epithelial cell healing, and corneal stem cells. These findings may trigger further research on the role of the NGF pathway in limbal stem cell deficiency. (Invest Ophthalmol Vis Sci. 2012; 53:8280‐8287) DOI:10.1167/iovs.12-1059