Study of New NO-Donor Compounds for the Potential Treatment of Glaucoma and Ocular Hypertension - CONCLUDED
Loretta Lazzarato
Barbara Rolando
Aree / Gruppi di ricerca
Partecipanti al progetto
- Arpicco Silvia (Ricercatore/trice)
- Blangetti Marco (Assegnista)
- Fruttero Roberta (Docente)
- Giorgis Marta (Ricercatore/trice)
- Lazzarato Loretta (Docente)
- Marini Elisabetta (Ricercatore/trice)
- Rolando Barbara (Docente)
Descrizione del progetto
Attività
Project Coordinator:
Nicoletta Almirante
Members of other units:
Alberto Gasco
NicOx Research Institute staff
Partners:
DSTF, University of Turin, Italy
NicOx Research Institute, Bresso, Italy
Sponsors:
NicOx Research Institute supported this scientific collaboration with a contribution of 70,000 euro.
Description
Glaucoma, a complex disease in which the optic nerve is damaged with consequent loss of visual function, is one of the major causes of visual impairment in the world. There are two principal kinds of glaucoma: open-angle glaucoma (primary glaucoma)(POAG), the most widespread form of the disease, and the closed-angle glaucoma. Elevated intraocular pressure (IOP) is the most important risk factor in the degeneration of optic nerve. Also oxidative stress seems to be implicated in glaucoma. According to some authors, compromised blood flow in retinal vessels induces production of reactive oxygen species (ROS) with consequent oxidative damage of retinal ganglion cells (RGCs). According to other authors the toxic effect of ROS is indirect since these species would serve as an early signal to mediate apoptosis. Increasing of IOP should induce decreased neurotrophin support to RGCs, so rendering these cells particularly sensible to ROS apoptotic signal.
Nitric oxide (NO) is a well known pleiotropic messenger which plays very important roles in the physiology and pathophysiology of mammalians. In particular deficiency of NO is involved in IOP rising and in the decrease of ocular blood flow. Some studies indicate that NO donors, which affect the NO-cyclic GMP pathway, are capable of lowering IOP in some animal and human experiments. Multitarget approach to the treatment of glaucoma has recently been proposed.
This project is aimed at developing new pharmacological tools for the treatment of glaucoma and ocular hypertension. It will be developed according to three different lines:
1) development of new NO-donors
2) development of hybrid drugs endowed with both the ability to release NO and with the capacity to display antioxidant action
3) development of formulations for the ocular delivery of drugs useful for the treatment of glaucoma
Keywords:
Glaucoma, Nitric oxide, IOP, Antioxidant