Dr. Yuri V. Kucheryavykh

Researcher: Dr. Yuri V. Kucheryavykh

Institution: Department of Biochemistry, Universidad Central del Caribe, Bayamón, Puerto Rico

Project Title: Polyamine Signaling via Glial Connexin-43 Hemichannels in Retina

AABRE Cluster:

Mentor: Dr. Parpura, Vladimir - Univ California Riverside

Collaborators and Consultants:

• Skatchkov, Serguei - Univ. Central del Caribe

Abstract:

Polyamine Signaling via Glial Connexin-43 Hemichannels in Retina The major glial cells in the retina, Müller cells, span the whole retinal thickness from photoreceptors to ganglion cells. Müller cells contact and even delimit all neuronal compartments and can release neuroactive substances to directly regulate neurons. One likely candidate to regulate retinal neuronal activity is the endogenous polyamine spermine (SPM). The polyamines spermine and spermidine (SPM/SPD) are predominantly located in Müller cells in the retina, but modulate many neuronal receptors and channels found on retinal neurons including AMPA, kainate, NMDA receptor channels and Kir channels. Our preliminary data demonstrate release of SPM/SPD from this glia to neuronal network under glial specific treatments.

Our working hypothesis is that endogenous SPM acts as a signaling molecule between glial and neuronal cells in the retina: (i) SPM is accumulated and released from Müller (glial) cells, potentially through unapposed hemi-gap junctions (hemichannels) and (ii) acts simultaneously on several types of neuronal receptors and channels to modulate retinal neuronal networks Using electrophysiological and immunocytochemical techniques, we propose to test this hypothesis by the following specific aims:

Specific aim 1– To determine if Müller glial cells express the biosynthetic enzymes necessary for polyamine synthesis under physiological and pathophysiological conditions.

Specific aim 2 – To examine SPM flux potentially through connexin hemichannels or P2X7 receptors in retinal Müller (glial) cells.

Specific aim 3 – To determine the effect of spermine on glutamate receptors in isolated retinal neurons and in a retinal whole-mount preparation. The results of these studies will provide insight into spermine-dependent retinal activity and may ultimately result in interventions for glaucoma, retinas ischemia, glutamate excitotoxicity and subsequent neuronal death.