Vascular Stroma Research Articles

Impairment of blood–cerebrospinal fluid barrier properties by retrovirus‐activated T lymphocytes: reduction in cerebrospinal fluid‐to‐blood efflux of prostaglandin E2

The choroid plexus epithelium forms the interface between the blood and the CSF. In conjunction with the tight junctions restricting the paracellular pathway, polarized specific transport systems in the choroidal epithelium allow a fine regulation of CSF-borne biologically active mediators. The highly vascularized stroma delimited by the choroidal epithelium can be a reservoir for retrovirus-infected or activated immune cells. In this work, new insight in the implication of the blood-CSF barrier in neuroinfectious and inflammatory diseases is provided by using a differentiated cellular model of the choroidal epithelium, exposed to infected T lymphocytes. We demonstrate that T cells activated by a retroviral infection, but not non-infected cells, reduce the transporter-mediated CSF-to-blood efflux of organic anions, in particular that of the potent pro-inflammatory prostaglandin PGE2, via the release of soluble factors. A moderate alteration of the paracellular permeability also occurs. We identified the viral protein Tax, oxygenated free radicals, matrix-metalloproteinases and pro-inflammatory cytokines as active molecules released during the exposure of the epithelium to infected T cells. Among them, tumour necrosis factor and interleukin 1 are directly involved in the mechanism underlying the decrease in some choroidal organic anion efflux. Given the strong involvement of CSF-borne PGE2 in sickness behaviour syndrome, these data suggest that the blood-CSF barrier plays an important role in the pathophysiology of neuroinflammation and neuroinfection, via changes in the transport processes controlling the CSF biodisposition of PGE2.

From multipotent stem cell to adipocyte

From multipotent stem cell to adipocyte

Cell binding isoforms of vascular endothelial growth factor-A (VEGF189) contribute to blood flow-distant metastasis of pulmonary adenocarcinoma

Vascular endothelial growth factor A (VEGF-A) has two kinds of isoforms depending on cellular binding domains. VEGF189 is the largest molecule with the strongest cellular binding ability, and is thought to be most potent for vascularization in various cancers. This study aims to clear the clinicopathological characteristics of VEGF189 in the pulmonary adenocarcinoma. We finely and quantitatively examined the expression of VEGF-A isoforms (VEGF121, VEGF165 and VEGF189) by real-time polymerase chain reaction in a total of 100 pulmonary adenocarcinomas resected by surgical operation. The VEGF isoform expression status was analyzed on clinicopathological features including stromal vascularization, vascular involvement, distant metastasis, lymph nodal metastasis, postoperative relapse time and prognosis of long-term observation periods. All the pulmonary adenocarcinomas showed significant expression of VEGF-A. Twenty-two cases with the adenocarcinomas overexpressing VEGF-A significantly showed earlier postoperative relapse and poorer prognosis between 5- to 15-year periods (p = 0.0093 and p = 0.0240, Kaplan Meier, log-rank test). The expression levels of VEGF189 increased in 13% of the pulmonary adenocarcinoma. These 13 cases with increased VEGF189 expression significantly showed higher distant metastases, earlier postoperative relapse, and poorer prognosis (p = 0.0006, Fisher's test; p = 0.0016 and p = 0.0084, Kaplan Meier, log-rank test) than the other 87 cases. The 13 lung cancers with VEGF189 overexpression also showed increased vessel counts, areas (p = 0.0091 and p < 0.0001, Mann-Whitney U test) and enhanced venous involvement (p = 0.0056, Fisher's test). The cellular binding isoform VEGF189 confers pulmonary adenocarcinoma patients with poorer prognosis with distant metastasis via blood flow.

Hepatobiliary Neuroendocrine Carcinoma in Cats: A Clinicopathologic, Immunohistochemical, and Ultrastructural Study of 17 Cases

Hepatobiliary neuroendocrine carcinoma was diagnosed in 17 cats in a period of 10 years. Seven tumors were of intrahepatic origin, one of which was a composite containing components of epithelial and neuroendocrine carcinoma. Nine tumors were of extrahepatic origin, and one tumor was located in the gall-bladder. The cats were adult and geriatric, and the male : female ratio varied according to tumor group. Hepatomegaly, anorexia, weight loss, and vomiting were the most common clinical signs observed in the cats with hepatic neuroendocrine carcinoma. The cats with extrahepatic neuroendocrine carcinoma showed these signs plus icterus (5/9) and high concentrations of hepatic enzymes. Histologically, the hepatic neuroendocrine carcinomas had two patterns, one with acinar structures separated by vascular stroma lined by cuboidal or columnar cells and the other solid with groups of anaplastic cells separated by vascular stroma. The composite tumor consisted of both bile duct carcinoma and neuroendocrine carcinoma. The extrahepatic neuroendocrine carcinomas and the gallbladder neuroendocrine carcinoma were characterized by solid sheets or groups of round to oval cells with vascular or fibrovascular stroma. Immunohistochemical examination of 10 of the neuroendocrine carcinomas revealed that all 10 stained with neuron-specific enolase; one bile duct carcinoma and the gallbladder carcinoma stained with chromogranin; four of five bile duct carcinomas and the gall bladder carcinoma stained with synaptophysin; and one bile duct carcinoma stained with gastrin. One cat with hepatic carcinoma had duodenal ulcer; in this cat, ultrastructural studies showed neurosecretory granules leading to the diagnosis of Zollinger-Ellison syndrome. In four cats in which necropsy was permitted, carcinomatosis (4/4), lymph nodes (4/4), lungs (2/4), and intestines (1/4) were the metastatic sites. Fourteen of the 17 cats were euthanatized during or immediately after surgery.

Benign Giant Cell Tumour of Tendon Sheaths in a European Lynx (Lynx lynx)

The histological, histochemical, immunohistochemical and ultrastructural features of a benign giant cell tumour (BGCT) of tendon sheaths in a 12-year-old male European lynx (Lynx lynx) are reported herein. The neoplastic mass involved the subcutaneous and inter-muscular tissues of the first, second, third and fourth digit of the left forelimb, from the phalanxes up to the carpus. The tumour appeared as a grey-whitish tissue mottled with darker areas, along with several scattered foci of orange colour. Histologically, the lesion consisted of a mixed population of numerous, multinucleated giant cells and epithelioid or spindle-shaped mononuclear cells embedded in a loose, highly vascular stroma. Neoplastic cells lined cleft formations and synovial-like projections into cystic spaces. No osteoid matrix could be detected. Haemorrhage and necrosis were also observed. The mononuclear and the giant cells were tartrate-resistant acid phosphatase and periodic acid-Schiff positive, being also immunohistochemically reactive for lysozyme and vimentin, with a few cells showing immunopositivity also for alpha-1-antitrypsin. Ultrastructurally, histiocyte-like cells, fibroblast-like cells and multinucleated giant cells were observed, but no virus-like particles could be detected in any of the above cell types. The BGCT of tendon sheaths, a fairly uncommon neoplasm in animals, has not been previously reported in the lynx.

Influence of Growth Hormone on Maintenance of Capillary‐like Structures in an In Vitro Model of Stromal Vascular Tissue—Results From Morphometric Analysis

The in vitro development of a vascular stroma might be a solution for the engineering of vascularized tissues, however, in vitro stability of capillary-like structures is limited. In order to test the influence on maintenance of capillary-like structures, human growth hormone (hGH) was added in concentrations of 0.5, 5, 50, and 500 ng/mL in an in vitro model of stromal vascular tissue. The angiogenic response and maintenance of capillary-like structures were analyzed by means of confocal laser scanning microscopy (CLSM) and image analysis after 8, 16, and 32 days of culture. The highest angiogenic response was observed with a concentration of 50 ng/mL hGH. With the addition of 50 and 500 ng/mL, the length of capillary-like structures could be maintained on high levels up to the 32nd day of culture, whereas with 5 ng/mL values dropped to the level of the control group. The proposed technique of analysis allows quantification of capillary-like network formation and might be useful for tissue engineering applications.

Oral inflammatory myofibroblastic tumor demonstrating ALK, p53, MDM2, CDK4, pRb, and Ki-67 immunoreactivity in an elderly patient

Inflammatory myofibroblastic tumor (IMT) is a controversial lesion composed of myofibroblasts, accompanied by varying numbers of inflammatory cells. Various pathogenetic factors have been proposed (ie, reactive, infectious, autoimmune, and neoplastic) but the etiology of most IMTs remains unknown. Here we review the literature of oral IMTs, detailing the demographic profile of these rare lesions. Moreover, we present an unusual case of IMT arising from the mandibular alveolar mucosa of an 82-year-old female. Microscopic examination revealed plump spindle cells set in a myxoid vascular stroma admixed with inflammatory cells. Numerous large ganglion cell-like cells were seen, some exhibiting emperipolesis of neutrophils. Ultrastructurally, prominent myofibroblasts with abundant rough endoplasmic reticulum were noted. Tumor cells were immunoreactive for vimentin, smooth muscle actin, and KP1 (CD68), and negative for desmin, S-100, and EBV-LMP. The lesion was excised without margins and the patient has manifested no evidence of disease at an 18-month recall. In an attempt to further delineate the potential neoplastic nature of this lesion, we assessed the immunohistochemical expression of various markers that have been linked to neoplastic transformation. The recorded positivity for ALK, p53, MDM2, CDK4, pRb, and Ki-67, despite the absence of bcl-2 reactivity, strongly favors the neoplastic origin of the studied tumor.

Histopathologic Features of Conjunctival Filtering Blebs

To characterize and compare the histological features of conjunctiva obtained during the repair of trabeculectomy and inadvertent blebs and to assess the effects of antifibrotic agents. We used routine paraffin processing and light microscopy to examine conjunctival specimens from 28 eyes undergoing late bleb revision: 19 leaking trabeculectomy blebs, 5 nonleaking trabeculectomy blebs, and 4 inadvertent blebs. Quantitative analysis of histological characteristics included conjunctival epithelial thickness, stromal vascularity, squamous metaplasia, stromal inflammatory cell infiltrate, and goblet cell density. The type of surgery, presence of leaks, prior topical medication, and antifibrotic use were correlated with histological findings. Trabeculectomy blebs (leaking and nonleaking) showed decreases in overall epithelial thickness (P<.02), goblet cell density (P<.001), and vascularity (P<.001) compared with inadvertent bleb controls. Conjunctiva exposed to antifibrotics had fewer layers of epithelial cells than those with no prior exposure (P<.05). Histological analysis of thin blebs excised following trabeculectomy demonstrated decreases in epithelial thickness and goblet cell density compared with inadvertent blebs. Both leaking and nonleaking trabeculectomy blebs exhibited decreases in localized stromal vascularity and increases in surrounding stromal vascularity compared with normal conjunctiva.

Ocular manifestations of keratitis– ichthyosis–deafness (KID) syndrome

Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital ectodermal dysplasia characterized by the association of hyperkeratotic skin lesions, moderate to profound sensorineural hearing loss and vascularizing keratitis. Mutations in the GJB2 gene coding for connexin 26, a component of gap junctions in epithelial cells, have been observed in several KID patients. Variable ocular manifestations of the disease in 3 patients with molecular genetically confirmed KID syndrome are reported. Retrospective case series. Clinical examination and molecular genetic analysis for mutations in the GJB2 gene were performed in 3 patients with KID syndrome ages 5, 13, and 41 years. Visual acuity ranged from normal to severe visual loss. The ocular signs included loss of eyebrows and lashes, thickened and keratinized lids, trichiasis, recurrent corneal epithelial defects, superficial and deep corneal stromal vascularization with scarring, keratoconjunctivitis sicca, and, in one patient, presumed limbal insufficiency. Whereas ocular surface integrity could be maintained with artificial tears in one patient, and an epithelial defect healed under conservative treatment in the second patient, multiple surgical procedures including superficial keratectomies, limbal allograft transplantation with systemic immunosuppression, amniotic membrane transplantation, lateral tarsorrhaphies, and lamellar keratoplasty could not preserve useful vision in the third patient. KID syndrome may affect the ocular adnexae and surface with variable severity independent of the age of the patient. Lid abnormalities, corneal surface instability, limbal stem cell deficiency with resulting corneal complications, and dry eye are the main ocular manifestations.

Morbus Castleman

A 25-year-old patient with fever, dysphagia, and reduced general condition was referred to our department by his dentist after 1 week of antibiotic therapy. He presented with a painful palpable mass in the right lower jaw that had developed 2 weeks before. The orthopantomogram showed a caries and periapical lesion at the right lower wisdom tooth. During extraction of the tooth and putative intra- and extraoral abscess incision, no pus could be drained and the mass persisted. CT scans then revealed lobulated soft tissue masses on both sides of the neck with the main focus on the right side. In an additional operation with excision of the mass, Castleman's disease of the hyaline vascular type was diagnosed. Staging could not detect further pathological findings and the patient's postoperative general condition improved continuously. The histological features of the hayline vascular type of Castleman's disease were characterized by multiple germinal centers surrounded by circumferentially arranged layers of small lymphocytes interconnected by a prominent vascular stroma with occasional plasma cells ("onion skin"). Castleman's disease is a rare and yet poorly understood disease, characterized by inhomogeneous growth of lymphoid tissue. Mostly benign it remains a diagnostic challenge before histological investigation. In unclear submandibular swellings and neck lumps assumed to be an abscess, this rare differential diagnosis must be considered. Facing recurrence and potential for malignancy, follow-up of the patients over several years is necessary.

Histopathological findings in a surgically resected thalamic cavernous hemangioma 1 year after 40-Gy irradiation

Stereotactic radiosurgery is a controversial treatment modality in the management of cerebral cavernous hemangiomas (CHs), and results vary from center to center. Even the interpretation of treatment failure is controversial. It is suggested that the systematic pathological investigation of irradiated specimens could help to resolve the controversy. A hemorrhagic lesion in the posterior part of the thalamus had been diagnosed as a tumor and was treated with 40-Gy fractionated radiotherapy. One year after this treatment the case was reconsidered based on new imaging evidence, and the lesion was removed by conventional craniotomy. Histopathological examination revealed a CH with postirradiation changes. Compared with nonirradiated control CH tissue samples, there was endothelial cell destruction and marked fibrosis with scar tissue formation in the stroma of the treated lesion. The histopathological findings in this specimen were similar to those described in arteriovenous malformations after gamma knife surgery. The results of light microscopic investigations suggest that the ionizing effect of radiation energy evokes vascular and connective tissue stroma changes in CHs as well.

Histopathological findings in a surgically resected thalamic cavernous hemangioma 1 year after 40-Gy irradiation

✓ Stereotactic radiosurgery is a controversial treatment modality in the management of cerebral cavernous hemangiomas (CHs), and results vary from center to center. Even the interpretation of treatment failure is controversial. It is suggested that the systematic pathological investigation of irradiated specimens could help to resolve the controversy. A hemorrhagic lesion in the posterior part of the thalamus had been diagnosed as a tumor and was treated with 40-Gy fractionated radiotherapy. One year after this treatment the case was reconsidered based on new imaging evidence, and the lesion was removed by conventional craniotomy. Histopathological examination revealed a CH with postirradiation changes. Compared with nonirradiated control CH tissue samples, there was endothelial cell destruction and marked fibrosis with scar tissue formation in the stroma of the treated lesion. The histopathological findings in this specimen were similar to those described in arteriovenous malformations after gamma knife surgery. The results of light microscopic investigations suggest that the ionizing effect of radiation energy evokes vascular and connective tissue stroma changes in CHs as well.

Inflammatory myofibroblastic tumor of the oral cavity: review of the literature and presentation of an ALK-positive case

Inflammatory myofibroblastic tumor (IMT) is a controversial lesion composed of myofibroblastic spindle cells accompanied by varying numbers of inflammatory cells. Although various pathogenetic (ie, reactive, infectious, autoimmune, and neoplastic) factors have been implicated, the etiology of most IMTs remains unknown. Here, we present a case of IMT arising from the mandibular alveolar mucosa of an 82-year-old female. The lesion presented as a 5 × 5 cm round pedunculated painless mass of 2 months' duration, associated with a superficial resorptive defect of the mandible. The lesion was surgically removed and, on histopathologic examination, appeared to be composed of plump spindle cells set in a myxoid vascular stroma admixed with an inflammatory component consisting primarily of neutrophils and lymphocytes. Numerous large “ganglion cell–like” cells were dispersed throughout the lesion. Only occasional mitotic figures were encountered, in the absence of cytologic atypia. Ultrastucturally, prominent myofibroblastic features were seen. Immunohistochemical analysis revealed that the spindle and ganglion-like cells were diffusely positive for vimentin, smooth muscle actin, and anaplastic lymphoma kinase (ALK), focally positive for CD68, and negative for desmin, bcl-2 and EBV-LMP. No evidence of recurrence has been noted at a 12-month follow-up. Including our patient, only 14 cases of oral IMT have been described in the literature. Patients' age ranged from 2 to 82 years with a mean of 35 years, and a 1.6:1 female predilection was noted. The buccal mucosa was the most commonly affected site (50%), followed by the mandible (21%). None of the reported cases of oral IMT recurred or metastasized. The present case is the second reported ALK-positive oral IMT, which points to a potential neoplastic origin. Significant differences in the clinical behavior and immunohistochemical and genetic profile of lesions diagnosed as IMT may indicate that the term has been used to describe lesions with similar histology but variable etiopathogenesis and prognosis.

P‐88 Endocrine dermatosis and granulosa cell tumour in a red panda

A 9‐year‐old red panda from the Vienna Zoo showed progressive hair loss of 2 years duration beginning at the tip of the tail and slowly spreading to the lower back, abdomen and thorax. Severe pruritus and mild automutilation was present only at the tail. Antifungal and antibiotic therapy showed little effect. Skin biopsies showed a thin hyperkeratotic epidermis, moderate superficial dermal sclerosis, mild superficial pyoderma, and complete atrophy of hair follicles and adnexae. Ultrasonography revealed an anechogenic circular mass 3 cm in diameter limited by echogenic trabeculae. The animal was euthanized. Necropsy revealed two smooth red‐brown soft solid nodules (3×3×2 cm) situated bilaterally at the caudal pole of the kidneys. Viscera, thyroid and adrenal glands as well as the uterus showed normal macroscopic and histologic appearance. Histologically, the pararenal nodules were recognized as enlarged ovaries with a small number of follicles and a large solid mass of slightly atypical vacuolated polygonal cells of Leydig‐cell character, which partly invaded the adjacent adipose tissue and were accompanied by discrete and strongly vascular stroma. Diagnosis of bilateral granulosa cell tumour was made. We concluded that the progressive hypotrichotic dermatosis was due to an endocrine abnormality. Funding: Self‐funded.

Commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage.

The increase of adipose tissue mass associated with obesity is due in part to an increase in the number of adipocytes. This hyperplasia results from recruitment of pluripotent stem cells present in the vascular stroma of adipose tissue. A model cell culture system has been developed that recapitulates this process both ex vivo and in vivo. After treatment of pluripotent C3H10T1/2 stem cells with bone morphogenic protein 4 (BMP4) during proliferation followed by differentiation inducers at growth arrest, the cells synchronously enter S phase and undergo mitotic clonal expansion, a hallmark of preadipocyte differentiation. Upon exiting the cell cycle, these cells express adipocyte markers and acquire adipocyte characteristics at high frequency. C3H10T1/2 cells treated with BMP4 in cell culture and implanted s.c. into athymic mice develop into tissue indistinguishable from adipose tissue in normal fat depots. We interpret the findings as evidence that BMP4 is capable of triggering commitment of pluripotent C3H10T1/2 stem cells to the adipocyte lineage.

Quantification of ovarian stromal Doppler signals in poor responders undergoing in vitro fertilization with three-dimensional power Doppler ultrasonography

ObjectiveThis was a prospective comparative clinical study to test the hypothesis that the decreased ovarian sensitivity to gonadotropins observed in women embarking on an in vitro fertilization (IVF) treatment may be due to changes in ovarian stromal blood flow. Study designThree-dimensional (3D) power Doppler ultrasonographic indexes were used to quantify ovarian stromal blood flow and vascularization in poor responders. Forty patients undergoing an IVF cycle were collected and divided into two groups, a poor responder group (n=17) (estradiol <600 pg/mL or ≤3 oocytes retrieved) and normal responder group (n=23), based on their response to a standard down-regulation protocol for controlled ovarian stimulation. During ovarian stimulation, on the day of administration of human chorionic gonadotropin (HCG), patients underwent hormonal (serum E2), ultrasonographic (follicular number and diameter), and 3D power Doppler (ovarian stromal blood flow) evaluation. ResultsCompared with poor responders, the serum estradiol levels on the day of administration of HCG, the number of follicles more than 14 mm, the number of oocytes retrieved, the number of embryos transferred, and the pregnancy rate were significantly higher in normal responders. The Vascularization Index, Flow Index, and Vascularization Flow Index were significantly lower (P<.05) in the poor responder (0.13±0.11, 30.89±10.35, and 0.05±0.04, respectively) compared with the women with a normal response (1.20±1.10, 43.88±7.77, and 0.61±0.57, respectively). ConclusionThe 3D power Doppler indexes of ovarian stromal blood flow in poor responders was significantly lower than normoresponders. This may help to explain the poor response during HCG administration in controlled ovarian stimulation.

Ribozyme mediated down-regulation of thrombospondin receptor CD36 inhibits the growth of the human osteosarcoma cell line

Thrombospondin-1 (TSP1) is known to possess tumor suppressor functions. In contradiction, TSP1 enhances the stromal vascularization and growth of certain cancers. A cell adhesion receptor, CD36, has been shown to interact with a ligand TSP1. We studied how CD36 affects the growth of the osteosarcoma cell line (HOS) expressing TSP1. We used the anti-CD36 ribozyme to specifically suppress CD36 gene expression in the HOS. The expression of the CD36 mRNA was significantly suppressed in the ribozyme-introduced cell line (HOS/Rz). The transformant HOS/Rz markedly decreased its growth. The growth of the osteosarcoma cell line HOS may be regulated by autocrine or paracrine loop TSP1 and CD36.

CANALICULAR ADENOMA ARISING IN THE UPPER LIP: REVIEW OF THE PATHOLOGICAL FINDINGS

This case report describes a rare case of canalicular adenoma arising in the upper lip of a 61-year-old male patient. Macroscopic examination of the tumor revealed a well-defined, smooth, firm, elastic hard, round nodule with a diameter of 1.0 cm. The cut surface was white. Histopathology showed that the tumor was an encapsulated mass with a complex cellular pattern of anastomosing duct-like or trabecular structures lined by a single layer of tall columnar epithelial cells, which were embedded in a loose, fibrous, and highly vascular connective tissue stroma. The tumor cells were immunoreactive to AE1/AE3, CK19 and S-100, were partially positive for CK7, CK8, GFAP and PCNA, but were negative for SMA, CK13, CK14 and vimentin.

Abnormal Autofluorescence Bronchoscopy Pattern in a Bronchial Lipoma

Autofluorescence bronchoscopy is currently used to detect the early stage of intraepithelial neoplastic lesions in patients at risk for lung cancer. We report a case of bronchial lipoma, a rare benign tumor, analyzed by autofluorescence bronchoscopy (AB), which revealed an autofluorescence abnormality showing a brownish-red colored area limited to the surface of a well-circumscribed mass in the superior segmental bronchus of the left lower lobe. Highly vascularized stroma and/or fatty subepithelial tissue could explain the autofluorescence abnormality of this bronchial lipoma. This case report emphasizes the potential role of AB in detecting nonneoplastic lesions such as angiogenic abnormalities.

Herpes simplex virus entry receptor nectin-1 is widely expressed in the murine eye

Purpose. Nectin-1 belongs to the immunoglobulin superfamily, mediates cell-cell adhesion in cadherin-based adherens junctions, and acts as a receptor for herpes simplex virus (HSV). The goals of this study were (1) to determine whether nectin-1 is expressed in ocular tissue that is an important target of HSV infections and (2) to determine whether HSV type 1 (HSV-1) infection affects nectin-1 expression in the eye. Methods. Expression of nectin-1 and HSV-1 protein was determined by immunohistochemical analysis of ocular tissues of untreated BALB/c mice and mice that were euthanized either 7 days or 7 months after corneal inoculation of HSV-1 or sterile tissue-culture medium (mock). Results. In ocular tissues derived from untreated and mock-infected mice, widespread nectin-1 expression was detected among cells of the corneal epithelium and endothelium, conjunctiva, lens epithelium, ciliary body, iris, choroid, and retina. However, fibroblasts in the corneal stroma and the sclera did not express detectable levels of nectin-1. Ocular tissues from mice euthanized 7 days after corneal inoculation of HSV-1 frequently demonstrated corneal ulceration and inflammation and HSV-1 protein expression in the corneal epithelium, stroma, endothelium, conjunctiva, iris, and ciliary body but rarely in the retina. Ocular tissues from mice euthanized 7 months after HSV-1 inoculation demonstrated corneal epithelial and stromal inflammation, but HSV-1 protein expression was not detected. HSV-1 infection did not lead to a loss of nectin-1 expression in any of the tissues examined. In contrast to uninfected corneas, the inflamed and vascularized stroma of infected corneas contained mononuclear inflammatory cells, vascular cells, and fibroblasts that stained positive for nectin-1. Conclusions. Findings report that nectin-1 is widely expressed in murine ocular tissues. Only fibroblasts in the corneal stroma and sclera of uninfected tissues were devoid of nectin-1 expression. HSV-1-infected inflamed corneas contained some stromal fibroblasts with detectable nectin-1 expression, which potentially could be targeted by the virus. Widespread nectin-1 expression in the eye suggests that this receptor may play a role in the pathogenesis of ocular HSV infections.