Abstract
Purpose: :
To test the hypothesis that endogenous zinc serves a cytoprotecitve role in the distal retina.
Methods: :
Co-release of zinc with glutamate from the synaptic terminals of photoreceptors has been demonstrated, and there is electrophysiological evidence indicating that zinc feeds back to suppress calcium entry and thereby reduce vesicular release of zinc and glutamate. This feedback may protect the retina from glutamate toxicity, especially in the dark when photoreceptors are maximally depolarized. To test this hypothesis, we used intra-ocular injection of 10µL of the zinc chelator TPEN (100µM) into the skate (Raja erinacea) eye. Control eyes were similarly injected with Ringer alone or with the glutamate agonist NMDA (500µM) which is known to induce glutamate toxicity in the inner retina of other vertebrates. Animals were maintained in darkness overnight prior to euthanasia and removal of the retinas for histological examination.
Results: :
Consistent with the results of earlier studies, intraocular injection of NMDA resulted in the disruption and loss of neurons in the inner retina; photoreceptors and RPE cells were relatively unaffected. The retina of the contralateral eye, which received a sham injection of Ringer, showed no signs of cytotoxicity. The retina of the eye injected with the zinc chelator TPEN showed evidence of glutamate toxicity similar to that of the NMDA treated eye, i.e., cytotoxicity is induced by the removal of endogenous zinc.
Conclusions: :
Reduction of retinal zinc by chelation results in histological damage to the inner retina typical of glutamate toxicity. This is an indication that the endogenous release of glutamate can cause retinal damage when left unchecked by zinc feedback. We suggest that zinc plays a cytoprotective role in the normal retina by down-regulating glutamate release from photoreceptors. This role is especially important during conditions of prolonged darkness, when photoreceptors are maximally depolarized and their neurotransmitter is maximally discharged.
Keywords: protective mechanisms