Stimulation of photoreceptor disc shedding and pigment epithelial phagocytosis by glutamate, aspartate, and other amino acids.
It has been reported that aspartate and glutamate selectively impair the structure (Olney, '82) and function (e.g., Furakawa and Hanawa, '55) of second- and third-order retinal neurons while leaving the photoreceptor unaffected. Either amino acid may mimic the endogenous photoreceptor neurotransmitter (Ehinger, '82). We report here that excitatory amino acids also induce massive rod photoreceptor disc shedding in eyecups of Xenopus laevis maintained in vitro. Disc shedding is the process whereby photoreceptors eliminate effete discs. It involves interaction between the distal outer segment and pigment epithelium. Millimolar L-aspartate and L-glutamate, as well as micromolar kainic acid, a glutamate analog, stimulate disc shedding three- to fivefold higher than normal light-evoked shedding levels and result in extensive inner retinal damage. Fifty-millimolar KCl, 1.0 microM ouabain, and replacement of sodium with choline also stimulate disc shedding and alter retinal structure. Extensive neurotoxicity appears unrelated to disc shedding since other amino acids having no significant or marginal effects on retinal structure also stimulate shedding. While the site and mechanism of action of these effectors, and in particular the excitatory amino acids, is now undefined, the data show that amino acids thought to act directly and specifically on inner retinal neurons can also markedly alter photoreceptor and pigment epithelial metabolism.
Greenberger
L M
LM
Besharse
J C
JC
D000596:Amino Acids / Q000633:toxicity*; D000818:Animals; D001224:Aspartic Acid / Q000633:toxicity; D002462:Cell Membrane / Q000473:pathology; D002794:Choline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000633:toxicity; D018698:Glutamic Acid; D007608:Kainic Acid / Q000633:toxicity; D007700:Kinetics; D009924:Organ Culture Techniques; D010042:Ouabain / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects*; D010775:Photic Stimulation; D010786:Photoreceptor Cells / Q000187:drug effects* / Q000473:pathology; D010857:Pigment Epithelium of Eye / Q000187:drug effects* / Q000473:pathology; D011189:Potassium Chloride / Q000494:pharmacology; D014982:Xenopus laevis
D000596:Amino Acids; D005971:Glutamates; D001224:Aspartic Acid; D018698:Glutamic Acid; D010042:Ouabain; D011189:Potassium Chloride; D002794:Choline; D007608:Kainic Acid