NEONATAL EXPOSURE TO D,L-2-AMINO-3-PHOSPHONOPROPIONATE (D,L-AP3) PRODUCES LESIONS IN THE EYE AND OPTIC-NERVE OF ADULT-RATS

Metabotropic glutamate receptors are a recently described receptor cla ss with emerging importance in synaptic plasticity and brain developme nt. Activation of metabotropic glutamate receptors results in several cellular secondary messenger events that are especially important duri ng postnatal development. This study characterized the effects of D,L- 2-amino-3-phosphonopropionate (D,L-AP3), an aspartic acid analog with agonist and antagonist activity at the metabotropic receptor, on the p ostnatal development of the rat eye and optic nerve. Sprague-Dawley ra t pups were treated daily (i.p.) with saline or 500 mg/kg D,L-AP3 on p ostnatal days (PND) 4-10 or 10-14. After making clinical and ophthalmo scopic examinations, rats were necropsied between 65 and 70 days of ag e and light microscopic evaluations were made of eyes and optic nerves . Between postnatal days 10-20, all treated rats exhibited motor tremo rs, circling, and head tilt. Ophthalmoscopic lesions were more severe in rats treated on days 4-10 than days 10-14 and included decreased re tinal vasculature, cataracts, and retinal dysplasia, hypoplasia, and d etachment. All rats treated on days 4-10 had severe optic nerve atroph y/hypoplasia grossly and severe retinal atrophy, retinal detachment, a nd cataracts histologically. Seven of eight rats treated on days 10-14 had qualitatively similar but less severe lesions. Overall, rats trea ted with D,L-AP3 on PND 4-10 had earlier and more severe retinal and o ptic nerve lesions when compared to rats treated on PND 10-14. These d ata characterize the morphologic effects in adult rats exposed to D,L- AP3 as neonates and suggest a possible role for the metabotropic recep tor in the postnatal development of retina and optic nerve.