Neurotropic Herpesvirus HSV-1 H129 Infection From Intraocular Pressure Baroreceptive Trigeminal Ganglion Nerve Endings Innervating The Rat Anterior Eye Chamber To The Nuclei Of Hypothalamus

PURPOSE: Neurotropic herpesvirus: cytomegalovirus(CMV)herpes simplex virus-1(HSV-1)and varicella zoster virus(VZV)infection in the anterior eye chamber(AEC)has been proposed to be the initial event that leads to Posner-Schlossman Syndrome(PSS).However,the relationship between virus infection in the AEC and intraocular pressure(IOP)elevation remains elusive.Our previous studies suggested that mechanosensitive trigeminal ganglion(TG)nerve endings innervating the inner wall of the AEC might play a role in baroreception of IOP.We speculated that the high IOP caused by herpesvirus infection was related to their neurotropism.This study was designed to determine whether the neurotropic herpesvirus could infect from the TG nerve endings distributing in the AEC to the nuclei of hypothalamus,the possible afferent pathway and modulation center of IOP neural control.METHODS: Using the anterior chamber microinjection technique,anterograde trans-multisynaptic viral tracer,enhanced green florescent protein(EGFP)expressing HSV-1 H129 was injected into the ACE of 10 SD rats,animals were fed for 6-9 days and then sacrificed when they showed signs of death,the TG and brain tissue were taken for frozen section,immunofluorescence staining was applied to enhance the fluorescence signals,and the fluorescence signals of the trigeminal ganglia and hypothalamus were observed under a fluorescence microscope.Employing the same method,the non-synaptic-transmitted fluorescent dye,1,1'-dilinoleyl-3,3,3',3'-tetramethylindo-carbocyanine,4-chlorobenzenesulfonate(FAST Dil)was injected into the ACE of 5 control SD rats.After 7 days,the trigeminal ganglion and brain tissue were obtained,then prepared for frozen section,fluorescence signals of the trigeminal ganglia and the hypothalamus were observed directly under a fluorescence microscope.RESULTS: For the 5 control rats,the FAST Dil(red)fluorescence signals were found in the ipsilateral trigeminal ganglion,and no fluorescence signal was observed in the hypothalamus.For the 10 rats in the experimental groups,the virus carrying EGFP(green)fluorescence signal was found in the ipsilateral trigeminal ganglion.Obvious green fluorescence signals can be observed in the hypothalamus in five of them,especially in the dorsal medial nucleus of the hypothalamus,the ventromedial nucleus and the paraventricular nucleus,and no fluorescence signal was showed in the hypothalamus of the other 5 rats,only a little green fluorescent signal can be observed in the spinal trigeminal nucleus.CONCLUSIONS: Our results indicate that the anterograde neurotropic herpesvirus could infect nuclei of hypothalamus from the TG nerve endings distributing in the AEC via TG,and the infection pathway may represent the afferent pathway,and the DMH/PeF,VMH and PVN nuclei of hypothalamus may play a role of modulation center of IOP neural control.Neurotropic herpesvirus interference with the function of the IOP baroreceptive TG nerve endings,the afferent pathway and modulation center of IOP neural control may contribute to the pathogenesis of PSS.