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U. Greferath, E. L. Fletcher, H. Ohtsu, M. Murphy; Histamine in the Development and Maintenance of the Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5942.
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The biogenic amine, histamine, and some of its receptors have been found in the retina of many mammalian species. However, little is known about the function of histamine in the retina. We have analysed mice mutants deleted for the gene for the histamine producing enzyme, histidine decarboxylase (HDC). These mutants specifically lack histamine. We made the surprising observation that these mice show an aberrant phenotype in the outer retina, reminiscent of photoreceptor degeneration diseases. We aim to characterize the nature and time course of disruption in retinae of HDC-KO mice in detail.
Wild-type and HDC-knockout mice from postnatal day 3 to 14 weeks of age were used. Retinae were aldehyde fixed and either paraffin embedded and Nissl stained, or stained as wholemounts or cryo-sectioned and processed for indirect immunofluorescence using antibodies targeted against specific cell types. Changes in photoreceptors and inner retinal neurons were examined. At 13-14 weeks fundoscopic images were taken of WT and HDC mice and retinal function was measured using a twin flash electroretinogram paradigm.
1. Immunohistochemistry revealed aberrations in the outer retina of the HDC-KO mice: the laminar structure of outer plexiform layer was disrupted by whorls of cells comprised mainly of recoverin positive photoreceptors. The inner layers of the retina appeared normal. In some retinal areas the outer nuclear layer was thinned implying photoreceptor loss. 2. Fundoscopy revealed aberrations only in ventral half of the retina, the dorsal half appeared normal. 3. Abnormalities in the retinae of HDC-KO could be observed as early as postnatal day 4 (P4) 4. Electrophysiological findings discovered reduced photoreceptor sensitivity in HDC-KO compared with WT.
Our data suggest that histamine is involved in the regulation of photoreceptor development and/or maintenance. The majority of human diseases resulting in blindness affect the photoreceptors. If we can understand the factors which regulate the development of photoreceptors, it may be possible to use this knowledge to develop effective treatments for regeneration of photoreceptors in blindness.
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