Neuronal Nitric Oxide Synthase Expresses in the Retinal Ganglion Cells and Endothelial Nitric Oxide Synthase in the Retinal Neurons in the Developing Human Retinas

Abstract

Purpose: To investigate the expression of three different isoforms of nitric oxide synthases (NOS) in the retinas of human embryos. Methods: Retinas of human embryos ranging from 10.5 weeks of gestation (wg) to 28 wg were sectioned and processed for immunohistochemistry with antibodies against three different isoforms of nitric oxide synthases. Results: We found no inducible nitric oxide synthase immunoreactivity (IR) in the retinas and the surrounding tissues. As early as 10.5 wg, neuronal nitric oxide synthase (nNOS)-IR strongly expresses in the cell bodies and axons of the retinal ganglion cells (RGC). At 17 wg, nNOS-IR neurons can also be detected in the innermost part of the inner nuclear layer and on photoreceptors. At 21 wg, nNOS-IR is stronger and more widely distributed in the photoreceptor layer, but at 28 wg, it is decreased in the photoreceptor layer. Endothelial NOS (eNOS) expresses in the blood vessels on the surface of retinas and in the choroid at 10.5 wg. At 17 wg, when the eNOS-IR blood vessels just enter the retinas at the optic disc, scattered eNOS-IR neurons are observed in the inner nuclear layer of temporal retinas. At 21 wg, when eNOS-IR blood vessels spread to the whole retina, eNOS-IR neurons can be found in the ganglion cell layer and the innermost of the inner nuclear layer of both temporal and nasal retinas. Conclusions: This study is the first report to show that eNOS expresses in some retinal neurons in addition to the endothelial cells of blood vessels. On the other hand, nNOS strongly expresses in RGC axons during early development of the human retinas. The results may imply that NO plays an important role in the development of visual system.