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Cyclic AMP Prevents Retraction of Axon Terminals in Photoreceptors Prepared for Transplantation: An In Vitro Study

From the Departments of Neurology and Neurosciences and Ophthalmology, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School, Newark, New Jersey.

PURPOSE. Cell transplantation has emerged as a possible remedy for degeneration and injury in the central nervous system (CNS). In the retina, photoreceptor transplantation is a potential treatment for retinal degenerative disease. Graft survival has been well documented, but evidence of functional recovery is lacking. A major obstacle to recovery of vision is lack of synapse formation between grafted photoreceptors and host bipolar and horizontal cells. A prior study demonstrated that photoreceptors prepared for transplantation undergo rapid morphologic changes, including retraction of axon terminals toward their cell bodies, away from potential synaptic partners, a phenomenon that may interfere with graft–host synaptic interaction after transplantation. In this study, prevention of retraction of photoreceptor axon terminals was possible by pharmacological intervention.

METHODS. Photoreceptor sheets, prepared by vibratome sectioning, and full-thickness retinas, harvested from adult porcine eyes, were maintained in culture and treated with either the cyclic adenosine monophosphate analogue 8-(4-chlorophenylthio)-cyclic 3',5'-adenosine monophosphate (CPT-cAMP), or forskolin, an adenylyl cyclase stimulant, for up to 48 hours.

RESULTS. Both CPT-cAMP and forskolin treatments successfully blocked retraction of photoreceptor axon terminals. This effect was not due to cell toxicity and was reversed after removal of treatment, indicating its specificity.

CONCLUSIONS. Pharmacological manipulation of photoreceptor axonal plasticity may improve graft–host synaptic interaction after subretinal photoreceptor cell transplantation.

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