Opiate and N-methyl-D-aspartate receptors in form-deprivation myopia.
Pharmacological studies have implicated retinal opiate pathways in the visual regulation of ocular growth. However, the effects of opiate receptor subtype-specific compounds on form-deprivation myopia (FDM) are inconsistent (Seltner et al., 1997), and may be mediated by non-opiate receptors. The purpose of this study was to test whether opiate receptor-inactive (D-) enantiomers elicit the same FDM-suppressing effect as their opiate receptor-active (L-) counterparts. Since some opiates are thought to act at NMDA receptors, we also tested whether NMDA receptor agonists and antagonists influence ocular growth or FDM. We found that both L- and D- enantiomers of morphine-like compounds (dextrorphanol and levorphanol, and D- and L-naloxone) were equally effective in blocking FDM. The NMDA receptor antagonists dextromethorphan, MK801, and AP5 also suppressed FDM. A single toxic dose of NMDA, that destroys many subtypes of amacrine cells (including those that synthesize the opioid peptide enkephalin), induced myopia and ocular enlargement in ungoggled eyes, and eliminated the ability of form-deprivation to enhance ocular growth. The NR-1 subunit of the NMDA receptor was localized to a narrowly stratified, intense stratum at approximately 50% depth in the inner plexiform layer, diffusely throughout the proximal inner plexiform layer, and to many somata in the amacrine and ganglion cell layers. These observations suggest that most effects of opiate receptor ligands on FDM in the chick are mediated by non-opiate receptors, which are likely to include NMDA receptors. NMDA as an excitotoxin transiently enhances ocular growth, but thereafter disables retinal mechanisms that promote emmetropization and FDM. These observations are consistent with a prominent role for pathways utilizing NMDA receptors in FDM and ocular growth-control.
Fischer
A J
AJ
Lions Sight Centre/Department of Anatomy/Neuroscience Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
Seltner
R L
RL
Stell
W K
WK
D000818:Animals; D000831:Animals, Newborn; D002645:Chickens; D005123:Eye / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D007150:Immunohistochemistry; D008024:Ligands; D008297:Male; D009019:Morphinans / Q000494:pharmacology; D009216:Myopia / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism* / Q000517:prevention & control; D016202:N-Methylaspartate / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology*; D011957:Receptors, Opioid / Q000378:metabolism / Q000502:physiology*; D012683:Sensory Deprivation / Q000502:physiology*; D014018:Tissue Distribution; D015349:Vision, Monocular / Q000502:physiology*
D008024:Ligands; D009019:Morphinans; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D016202:N-Methylaspartate