Ocular and Lacrimal Gland Lesions in Naturally Occurring Rabies of Domestic and Wild Mammals

Abstract

Investigations describing the ocular and lacrimal gland lesions associated with rabies are sparse. Here we characterize the pathological changes and distribution of rabies viral antigen in the eye, optic nerve, and lacrimal gland of 18 rabies cases from different mammalian species. Histology and immunohistochemistry for rabies virus, CD3, CD20, and Iba1 were performed on tissue sections of eye, optic nerve, and lacrimal gland. Polymerase chain reaction (PCR) for rabies was performed on all cases, including 7 formalin-fixed, paraffin-embedded (FFPE) and 11 frozen tissue samples of eye and lacrimal gland. Pathological changes in the eye consisted of retinal necrosis (12/18 cases) with occasional viral inclusions within ganglion cells (8/12 cases). Immunohistochemically, viral antigen was detected within the nerve fiber layer, ganglion cells, and inner plexiform layer in all 12 cases with retinal lesions and in 2 cases with no retinal lesions, as well as optic nerve (6/18 cases) and lacrimal gland epithelium (3/18 cases). CD3+ T lymphocytes were present in the retina (11/18 cases), optic nerve (2/18 cases), and lacrimal gland (11/18 cases). No CD20+ B lymphocytes or Iba1+ macrophages were detected. PCR for rabies virus was positive in 9 of 11 frozen samples but in only 2 of 7 FFPE samples. Five samples that were negative for rabies by PCR were positive by immunohistochemistry, and 2 samples were negative by both tests. These results provide evidence that rabies virus infection extends to the eye, likely via the ocular nerve, and that the lacrimal gland might be a source of viral infection.

Neuroglia Infection by Rabies Virus after Anterograde Virus Spread in Peripheral Neurons

“…Virus detection in the orbital, nasal, and oral cavity confirmed previous reports about presence of RABV and related lyssaviruses in a variety of other tissues [17,30,22,1], including retinal ganglion cells, their axons, and lacrimal glands [25,15]. Considering the latter, a potential role of lacrimal glands in virus secretion has been discussed [15]. Whereas lacrimal fluid may not contribute to the transmission of infectious virus to new hosts via saliva, multiple infected sensory neurons in the olfactory and tongue epithelia (Fig.…”

“…Prolonged replication of pathogenic RABV in the brain eventually leads to the onset of a progressive rabies encephalitis, invariably resulting in the fatal disease progression. In animals suffering from RABV encephalitis, the virus can be detected in multiple nervous or innervated tissues including hind leg, spinal cord, brain, face, and salivary glands [5,15]. For the transmission of infectious virus to new hosts via virus-containing saliva, centrifugal spread of RABV in the peripheral nervous system (PNS) is required [18].…”

Neuroglia infection by rabies virus after anterograde virus spread in peripheral neurons

“…Virus detection in the orbital, nasal, and oral cavity confirmed previous reports about presence of RABV and related lyssaviruses in a variety of other tissues [ 1 , 17 , 22 , 30 ], including retinal ganglion cells, their axons, and lacrimal glands [ 15 , 25 ]. Considering the latter, a potential role of lacrimal glands in virus secretion has been discussed [ 15 ]. Whereas lacrimal fluid may not contribute to the transmission of infectious virus to new hosts via saliva, multiple infected sensory neurons in the olfactory and tongue epithelia (Figs.…”

“…Prolonged replication of pathogenic RABV in the brain eventually leads to the onset of a progressive rabies encephalitis, invariably resulting in fatal disease progression. In animals suffering from RABV encephalitis, the virus can be detected in multiple nervous or innervated tissues including hind leg, spinal cord, brain, face, and salivary glands [ 5 , 15 ]. For the transmission of infectious virus to new hosts via virus-containing saliva, centrifugal spread of RABV in the peripheral nervous system (PNS) is required [ 18 ].…”