Retinal serotonin, eye growth and myopia development in chick

Myopia (short-sightedness) is a visual problem associated with excessive eye growth and vitreous chamber expansion. Within the eye serotonin (5-hydroxytryptamine, 5-HT) appears to have a variety of effects, it alters retinal amacrine cell processing, increases intraocular pressure, constricts ocular blood vessels, and is also mitogenic. This study sought to determine the role of the retinal serotonin system in eye growth regulation. Myopia was produced in 7-day-old chicks using −15 D spectacle lenses (LIM) and form deprivation (FDM). The effect on LIM and FDM of daily intravitreal injections of a combination of 5-HT receptor antagonists (1, 10, 50 μM), 5-HT2 selective antagonist (Mianserin 0.5, 20 μM) or 5-HT (1, 10, 50 μM) were assessed. Counts were performed of serotonin and tyrosine hydroxylase positive neurons and the relative density used to account for areal changes due to eye growth. The effect of LIM and lens-induced hyperopia (LIH) on the numbers of 5-HT-containing amacrine cells in the retina were then determined. The combination of 5-HT receptor antagonists inhibited LIM by approximately half (1 μM RE: −7.12±1.0 D, AL: 0.38±0.06 mm vs. saline RE: −13.19±0.65 D, AL: 0.64±0.03 mm. RE: p<0.01, AL: p<0.01), whereas FDM was not affected (1μM RE: −8.88±1.10 D vs. saline RE: −9.28±1.38 D). The selective antagonist was slightly less effective at inhibiting LIM (0.5 μM RE: −9.02±1.01 D). These data suggest that serotonin has a stimulatory role in LIM, although high doses of serotonin were inhibitory (1 μM RE: −9.30±1.34 D). 5-HT immunoreactivity was localised to a subset of amacrine cell bodies in the inner nuclear layer of the retina, and to two synaptic strata in the inner plexiform layer. LIM eyes had increased numbers of 5-HT-containing amacrine cells in the central retina (12.5%). Collectively, these results suggest that manipulations to the serotonin system can alter the eye growth process but the role of this transmitter system within this process remains unclear.