Glaucoma is one of the leading causes of bilateral blindness. Although in the past the criteria used for the diagnosis of the disease have led to some inconsistencies in the epidemiological reports, the data are actually quite impressive. It has been calculated that by 2010 more than 8 millions people will suffer, worldwide, of bilateral blindness associated with glaucoma; it is believed that the prevalence will increase further by the year 2020, when the prediction is esteemed around 11 millions of affected people.
The higher prevalence expected is associated to the aging of the population; in fact, glaucoma mainly affects the elderly. The picture becomes even more dramatic when the data are divided by geographical areas: the disease has a catastrophic impact in the developing countries and it is a serious clinical and economical concern for the industrialized countries. The situation is even more complicated by the limited therapeutic approaches available.
Glaucoma is a progressive optic neuropathy characterized by excavation of the optic nerve head and progressive loss of the visual field. The loss of nerve fibers is related to the death of retinal ganglion cells (RGCs) that, with their axons, form the optic nerve.
The causes underlying the death of RGC is still unknown although the increase of intraocular pressure (IOP) is considered the main glaucoma risk factor.
Therefore the reduction of IOP is the only therapeutic strategy currently used to slow the progression of the neuropathy. Paradoxically, about 90% of the population with elevated IOP does not develop glaucoma and, on the other hand, 33% of glaucoma patients does not show any increased IOP.
The multifactorial etiology of the disease explains the difficulties for the researchers to develop a genetic model of glaucoma. Despite that, the availability of both acute and chronic animal models that mimic the increase of IOP, provides useful tools to develop pathogenetic hypothesis and therefore new therapeutic approaches for neuroprotection of RGCs. However, the results obtained in the last ten years of research have been disappointing. Indeed, clinical trials and new neuroprotective molecules led to unsatisfactory results showing that additional studies are needed.
Recently, neurochemical investigations made by an intraocular microdialysis technique using an experimental model of glaucoma developed by the research team of neurotoxicology coordinated by Prof. Luigi A. Morrone have shown how the accumulation of extracellular glutamate, an amino acid recognized as the principal excitatory neurotransmitter, is implicated in neurodegeneration and death of RGCs.
The development of new therapies for glaucoma focused on a neurotrophic strategy, like the one pursued by our research group, is the basis of a two-year research agreement between the Section of Preclinical and Translation Pharmacology of Unical and the Maugeri Foundation of Pavia. The Maugeri Foundation will finance the studies of Prof. Luigi A. Morrone in collaboration with Dr. Rossella Russo.
The effectiveness of the research approach proposed by our team is supported by a recent study published on the Proceedings of the National Academy of Sciences U.S.A. (PNAS), that stems from the collaboration of the ophthalmologists of “Tor Vergata” University, the Gian Battista Bietti Foundation and the European Brain Research Institute Foundation of Rome under the coordination of Prof. Stefano Bonini. The study shows neuroprotection afforded by a three month to pic application of nerve growth factor (NGF), discovered by Prof. Rita Levi Montalcini, in glaucoma patients. The results are promising though they need to be further confirmed by a randomized clinical trial conducted on a relevant number of patients.