Expression Of NPR-A In Developing Eye Of Mouse

NPR-A is an important part of natriuretic peptide family, which is also a guanylatecyclase-coupled receptor. By combining with natriuretic peptides and elevating levels of intracellular cGMP,it mediates the physiological effects of natriuretic peptides. In the past, the study of the natriuretic peptidesystem is mainly focused on the cardiovascular system and central nervous system. Recently, natriureticpeptides are found widely expressed and play an important role in the eyes. Firstly, as a part of the centralnervous system, the retina extensively express natriuretic peptides, and which may control the transmissionof retinal nerve signals. Secondly, natriuretic peptides are also highly expressed in other parts of the eye,such as the aqueous humor, ciliary body. And they may regulate the intraocular pressure and control theprogress of glaucoma and other eye diseases. But now, there are still a lot of controversies on the positionand function of natriuretic peptides and their receptors in the eye. Especially, the research in the cornea andlens is very limited. In addition, the previous research has always focused on the adult eye, but nosystematic study of embryonic eye in the country. So the experiment attempted to detect the expression ofNPR-A by immunohistochemistry in mouse cornea, lens and retina from embryo to adult, and explore itssignificance in maintaining eye development and visual form, then give us a better understanding of thenatriuretic peptide system and provide new information for the treatment of retinal diseases!Purpose: Our purpose is to investigate the expression of NPR-A in the mouse cornea, lens andretina, and to discuss the following three aspects:①The NPR-A’s functions in the cornea development, aswell as the maintenance of corneal epithelial cells repair during the mouse development.②The importantregulatory functions of NPR-A in lens development, lens epithelial cell proliferation and the permeabilityof the lens.③The important regulatory role in the development of retinal neurons and the functionalactivity of Müller cells.Methods: Paraffin section immunohistochemistry, ink perfusion and stretchedimmunofluorescence techniques are carried out to observe the morphological changes in embryonic andpostnatal mouse cornea, lens and retina. And the density of NPR-A positive retinal photoreceptor cellsprojections were measured. Results:1. Expression of NPR-A in CorneaIn the embryo, NPR-A was highly expressed in embryonic corneal epithelial cells, and itcontinued to express until adulthood. However, P14afterward, its expression in the corneal stroma andendothelium layer was decreased gradually with age increasing. At as early as E16, NPR-A was expressedstrongly in the corneal epithelium, and continued to express at P5, P14and adulthood as well. Meantime,NPR-A could also be expressed in the corneal stroma and endothelial cells at E16. The expressionincreased and reached its peak at P5, then, it reduced gradually. After P14, only sparsely fibroblasts andendothelial cells were NPR-A positive.2. Expression of NPR-A in lensAt P0, NPR-A could be found in the anterior capsule epithelial cells. Then, its expressiondecreased and finally remained its expression only in the central epithelium cells at P90. In the lens fibercells, NPR-A could alsobe found in collagenous fibers and fibroblast in lens at as early as E16, and itsexpression was abundant at P0. Then, the NPR-A expression decreased from periphery to center at about P7,finally, it totally disappeared at P90. Meanwhile, the morphology of NPR-A positive fibroblasts are alsochanging. At P0, fibroblasts in anterior pole showed larger and irregular polygonal shape. At P3, the cellbodies of fibroblasts extended into the spindle-like shape, and P7afterward, all the fibroblasts becameelongated.3. Expression of NPR-A in retinaNPR-A was widely expressed in the retinal neurons. In the outer nuclear layer, NPR-A began toappear in the inner and outer projections of cone and rod cells at P7, but decreased at P14. P30afterward, itcontinued to express weakly. In inner nuclear layer, NPR-A expressed in the dendrites of bipolar cellsweakly from P7to adulthood, but no expression in horizontal cells. In the ganglion cell layer, NPR-Astarted to express in the ganglion cell bodies highly at E16. in the meantime, in the nerve fiber layer,ganglion cell axons, NPR-A was expressed highly from embryonic to adult. In the inner and outerplexiform layers, NPR-A was highly expressed at P14, but decreased gradually after P30. Besides, NPR-Aalso widely expressed in the inner protrusions of Müller cells, and continued into adulthood.Conclusion: In the cornea, NPR-A may be involved in the development of cornea and plays animportant role in corneal epithelial cell proliferation and lens repair. In the lens, NPR-A participates in the early development of the lens. In addition, it may be involved in epithelial cell proliferation and metabolicphysiology in adulthood, so the transparency of lens is probably regulated by NPR-A as well. In retina, onthe one hand, NPR-A may participate in the development of retinal neurons and regulate the migration anddifferentiation of neural cells, on the other hand, it plays an important regulatory role in the functionalactivity of Müller cells.