Excitatory amino acids interfere with normal eye growth in posthatch chick

Abstract

This study examines the effects of excitotoxic amino acids on eye growth and retinal morphology. Day old chicks received a single intraocular injection of either 200 nmoles kainic acid (KA), 200 nmoles quisqualic acid (QUIS) or 400 nmoles N-methyl-D,L-aspartate (NMDA). Following survival periods of 7, 14 and 21 days, eyeballs were removed and weighed. Measurements of axial length, equatorial length, anterior chamber depth and corneal diameter were taken. Treatment with KA increased eye weight and equatorial length. Treatment with QUIS increased the anterior chamber depth but decreased the equatorial length. Treatment with NMDA increased anterior chamber depth, but to a lesser extent than QUIS. The effects of QUIS and NMDA could be distinguished from those of KA since the former excitotoxins resulted in a marked increase in anterior chamber depth with no enlargement of vitreal chamber. Changes in eye size were evident by day 7 and were sustained throughout the duration of the experiment. Examination of retinae revealed that KA lesions amacrine cells, bipolar cells, some ganglion cells and photoreceptors. Exposure to QUIS lesions amacrine cells, horizontal cells and causes mild disruption of photoreceptor outer segments. In contrast, NMDA predominantly lesions amacrine cells. The results demonstrate that these neurotoxins have different effects on eye growth, which may be associated with differences in retinal pathology. It is proposed that photoreceptors are ideally suited to play a role in the control of eye growth.

Immunocytochemical characterization of quisqualic acid- and N-methyl-D-aspartate-induced excitotoxicity in the retina of chicks

“…Similar results have been described in other studies on chick retina using a single dose of NMDA or QA (Sattayasai and Ehrlich, 1987;Barrington et al, 1989;Sheppard et al, 1991). There are several possibilities to explain the tolerance of these cells.…”

“…This retinal degeneration closely matches qualitative aspects of NMDA-or QAinduced IPL degeneration reported previously in the chick eye (Sattayasai and Erhlich, 1987;Barrington et al, 1989;Erhlich et al, 1990;Sheppard et al, 1991). Similarly, Dvorak and Morgan (1983) reported that kainic acidinduced retinal thinning due to the permanent removal of neurons is stabilized 1 week after treatment.…”

“…It is currently believed that retinal modulation of ocular growth is mediated by subpopulations of amacrine cells, including those that release or respond to acetylcholine, dopamine, vasoactive intestinal polypeptide (VIP), and enkephalin (ENK; Wallman, 1993;Seltner and Stell, 1995;. The administration of a large dose of NMDA or QA to the chick retina has been shown to leave photoreceptor, bipolar, and ganglion cells intact but to destroy many amacrine cells (Morgan, 1987;Barrington et al, 1989;Ehrlich et al, 1990;Tung et al, 1990;Sheppard et al, 1991). The specific subsets of amacrine cells that are sensitive to NMDA or QA have not been identified.…”

Dopamine antagonists and brief vision distinguish lens-induced- and form-deprivation-induced myopia

“…This evidence for differing growth control mechanisms mediating anterior chamber versus vitreous chamber growth is in accord with similar reported effects of other molecules: the nitric oxide synthase inhibitor L-NAME (Nickla and Wildsoet, 2004), the retinal hormone melatonin (Summers Rada and Wiechmann, 2006), and kainic acid (Wildsoet and Pettigrew, 1988) all have dis-inhibitory effects on the back of the eye and inhibitory effects on the front, similar to our result with spiperone. By contrast, insulin (Feldkaemper et al, 2009) and quisqualic acid (Barrington et al, 1989) result in increases in anterior chamber growth but little or no change in growth of the back of the eye, again, supporting different mechanisms. Because both D1 and D2 receptors are found in the anterior segment of the eye, it is likely that dopamine plays a role in aqueous flow dynamics (Potter, 1995), which might be related to the effect reported here for spiperone.…”

Kainic Acid and Formoguanamine Effects on Environmentally-Induced Eye Lesions in Chicks

“…The retinal neurotoxin kainic acid (KA), and a similar compound, quisqualic acid (QUIS), seem to owe their blinding capabilities to the fact that they are both amino acid analogs which, like their normally metabolised counterparts, seek out certain classes of neurons and affix themselves, with excitatory effect (12)(13)(14). These neurotoxins were administered intravitrially, 200 nM in 10U.L of saline.…”