Background. Glaucoma (GL) is the world's leading cause of irreversible blindness and nowadays there are no treatments that improve visual outcome in glaucomatous patients.
Nerve Growth Factor (NGF) is the first discovered and best defined neurotrophic factor, it belongs to neurotrophins' (NTs) family and currently represents the most promising future approach for the identification, treatment and monitoring of ophthalmological diseases.
Evidences from both experimental and clinical studies show that NGF may prevent apoptosis and stimulate nerve cells recovery in retinal and optic nerve (ON) diseases, including GL.
The introduction of neuroprotective and neuroregenerative treatments would pave the way for a succesful management of these diseases.
Purpose. The present study aims to evaluate the potential of NGF and its precursors as biomarkers of disease progression in GL and to investigate the different profiles of NGF and NTs in glaucomatous population in order to identify patients candidate for NGF treatments.
Design. Prospective, cross-sectional study.
Methods. Patients fulfilling diagnostic criteria for early GL (n. 5), moderate GL (n. 5), advanced GL (n. 5) and normal age-matched controls (n. 15) will undergo a complete ophtalmological evaluation including morpho-functional visual examinations. Partecipants will be followed for one year characterizing the NGF pathway and NTs' profile associated with clinical parameters, tears and conjunctival epithelium collection as well as blood sample for NGF and NTs detection.
Results. Levels of NGF, NTs and their precursors and receptors will be evaluated in GL patients' peripheral blood, tears and conjunctival epithelium to identify both biomarkers predictive of GL outcome and a target population of NTs treatment.
In many cases, eye diseases such as GL constitute a healthcare need that currently available treatments are unable to meet. Several evidences [1-5] showed that NGF and/or NGF based compound represent an emerging treatment for glaucoma and the identification of potential diagnostic and prognostic biomarkers for disease could pave the way for personalized medicine.
Furthermore, the contribution of NTs and their receptors to disease processes, let us hypothesize that characterizing their profiles it will be possible to shed light on the pathophysiology of GL.
This study will characterize the role of NGF pathway in patients with GL in order to clarify the pathogenic role of NGF pathway and NTs and to identify potential biomarker for disease progression. GL is the leading cause of irreversible blindness in the world. It is characterized by RGCs degeneration and chronic loss of ON axons with progressive VF deficits and a consequent loss of visual function.
The only way we currently know to prevent and/or delay progression of ON degeneration in GL patients is by reducing IOP, the only modifiable risk factor but there is no treatment available that restores neural function. In addition, there are no biomarkers to early identify glaucomatous patients who are at risk for disease progression. Convincing evidences suggest that NGF plays a role in GL, in fact it provides trophic support to the RGCs and represents a potential biomarker and therapeutic agent for GL.
This study will allow to clarify the pathogenic role of NGF pathway and NTs in patients with GL in order to identify potential biomarkers of disease severity and progression and/or response to treatments. The increasing understanding of mechanisms concerning GL development may lead to a better management of patients with improvements in clinical outcomes and quality of life and, as consequence to a cost saving for the National Health System (NHS).
In fact, the identification of novel biomarkers of disease progression would result in a better management of these patients with improvements both in clinical outcomes with a reduced need of medical and personal assistance, and in patients¿ quality of life and ability to perform daily activities including work.
At the same time, our results are expected to have a major impact on basic research, clinical knowledge, and pharmaceutical industry, since they will identify GL patients population that could benefit by novel therapeutic interventions to be confirmed in subsequent clinical trials.
The results of the present project will advance knowledge on clinical science in ocular physiopathology and disease treatment. Specifically, the study will define the involvement of NGF pathway in patients with GL a challenging and potentially blinding disease
1. Lambiase A et al. Nerve growth factor delays retinal degeneration in C3H mice. Graefes Arch. Clin. Exp. Ophthalmol, 1996. 234: p. 96-100.
2. Lambiase A et al, Nerve growth factor (NGF) reduces and NGF antibody exacerbates retinal damage induced in rabbit by experimental ocular hypertension. Graefes Arch. Clin. Exp. Ophthalmol., 1997. 235(12): p. 780-785.
3. Colafrancesco et al, Ocular application of nerve growth factor protects degenerating retinal ganglion cells in a rat model of glaucoma. J. Glaucoma, 2011. 20(2): p. 100-108.
4. Lambiase A et al. Experimental and clinical evidence of neuroprotection by nerve growth factor eye drops: Implications for glaucoma. Proc Natl Acad Sci USA, 2009. 106(32): p. 13469-13474.
5. Oddone F et al. Exploring Serum Levels of Brain Derived Neurotrophic Factor and Nerve Growth Factor Across Glaucoma Stages. PLoS One, 2017. 12(1): p. e0168565.