Project: Gap junctions serve to distribute health-signals among neurons of the diseased retina

Acronym	Rethealthsi (Reference Number: NEURON-066)
Duration	01/05/2021
Project Topic	Gap junctions (GJ) have been found in the retina almost 40 years ago and their crucial role in signaling has repeatedly been proven. GJs have also been reported to serve a mechanism known as bystander effect by which neurons in the degrading tissue spread apoptosis via the enigmatic ‘death-signal’ molecule to their neighbors. It has therefore been proposed that a GJ blockade could serve to rescue neurons in progressive retinal diseases such as diabetic retinopathy, ischemia or glaucoma. However, GJs also serve as conduits of neuronal signals between neurons thus their chronic blockade would result in a loss of visual function. Therefore, we propose that GJs could be utilized as tools that promote neuron survival by the intercellular passage of rescue molecules rather than the ‘death-signal’. In this scheme the delivery of rescue molecules (‘health-signals’ in this proposal) would be followed by the cell-to-cell spreading of the compound through retinal GJs. The hypothesis works only if ‘health-signal’ molecules bear with a size, charge and 3D structure that allows them to travel across GJs. In this study we utilize GJ coupled retinal cellular networks to test the feasibility of transjunctional diffusion of epigenetic factors (miRNA transcripts), second messengers of intercellular cascades (IP3, cAMP, cGMP, Ca++) and clinically active compounds (Dexamethasone). Such spreading has a great potential to enhance effects of gene therapy of various neurological diseases.
Network	NEURON Cofund
Call	Call for Proposals for Transnational Research Projects on Sensory Disorders

Project partner

Number	Name	Role	Country
1	University of Pecs	Coordinator	Hungary
2	Carl von Ossietzky Universität Oldenburg	Partner	Germany
3	Policlinico Universitario Agostino Gemelli IRCCS	Partner	Italy