Ocular Histopathology Research Articles

Ocular Pathology Relevant to Glaucoma in aGja1Jrt/+Mouse Model of Human Oculodentodigital Dysplasia

Oculodentodigital dysplasia (ODDD) is a human disorder caused by mutations in the gap junction alpha 1 (GJA1) gene encoding the connexin43 (Cx43) gap junction protein. Causal links between GJA1 mutations and glaucoma are not understood. The purpose in this study was to examine the ocular phenotype for Gja1(Jrt/+) mice harboring a Cx43 G60S mutation. METHODS; In young Gja1(Jrt/+) mice, Cx43 abundance was assessed with a Western blot, and Cx43 localization was visualized using immunohistochemistry and confocal microscopy. Intraocular pressure (IOP) was measured by rebound tonometry, and eye anatomy was imaged using ocular coherence tomography (OCT). Hematoxylin and eosin (H&E)-stained eye sections were examined for ocular histopathology related to the development of glaucoma. Decreased Cx43 protein levels were evident in whole eyes from Gja1(Jrt/+) mice compared with those of wild-type mice at postnatal day 1 (P = 0.005). Cx43 immunofluorescence in ciliary bodies of Gja1(Jrt/+) mice was diffuse and intracellular, unlike the gap junction plaques prevalent in wild-type mice. IOP in Gja1(Jrt/+) mice changed during postnatal development, with significantly lower IOP at 21 weeks of age in comparison to the IOP of wild-type eyes. Microphthalmia, enophthalmia, anterior angle closure, and reduced pupil diameter were observed in Gja1(Jrt/+) mice at all ages examined. Ocular histology showed prominent separations between the pigmented and nonpigmented ciliary epithelium of Gja1(Jrt/+) mice, split irides, and alterations in the number and distribution of nuclei in the retina. Detailed phenotyping of Gja1(Jrt/+) eyes offers a framework for elucidating human ODDD ocular disease mechanisms and evaluating new treatments designed to protect ocular synaptic network integrity.

CASE REPORT: Iridociliary melanoma with secondary lens luxation: distinctive findings in a long‐horned cowfish (Lactoria cornuta)

This report describes a long-horned cowfish, which was diagnosed with buphthalmia and lens sub-luxation in the right eye, conditions that progressed to complete anterior lens luxation and secondary keratoconus. Three months after the initial evaluation, a pigmented mass was observed protruding from the vitreous. An enucleation was performed under general anesthesia. Ocular histopathology revealed an iridociliary melanoma. Reports of intraocular melanomas are extremely rare in fish. To the authors' knowledge, this is the first report of an iridociliary melanoma that led to buphthalmia, lens luxation, and keratoconus in a fish. Histological findings of lens luxation are also demonstrated. Due to the presence of a complex suspensory apparatus involving the teleost lens, this report speculates that lens luxation is a more devastating disease process in teleosts than in mammals.

LX211 (Voclosporin) Suppresses Experimental Uveitis and Inhibits Human T Cells

To test the therapeutic effectiveness of voclosporin against experimental autoimmune uveoretinitis (EAU) in rats and to evaluate its effect on human T cells. EAU was induced by immunization with a uveitogenic protein. Voclosporin administration, by subcutaneous injection, began on day (d) 0 or d7 after immunization. Treatment effectiveness was evaluated in vivo using clinical EAU scoring (d7-d13) and histopathologic evaluation of enucleated eyes after experimental termination. Rodent lymphocytes were harvested from lymph nodes on d14 for antigen-specific proliferation assays. The effect of voclosporin on human T-cell proliferation and cytokine secretion was examined in vitro. Voclosporin prevented EAU development in rats receiving medium and high preventive doses, whereas high-dose voclosporin administration effectively treated EAU. Lymphocytes from animals treated with voclosporin had decreased antigen-specific proliferation in vitro compared with lymphocytes from untreated animals. No evidence of abnormal ocular histopathology was found in the eyes from animals that received high doses of therapeutic voclosporin. Using human T cells, voclosporin inhibited human T-cell proliferation up to 100-fold. Furthermore, voclosporin treatment of human T cells significantly reduced pan T-cell effector responses. Voclosporin effectively suppressed uveoretinitis in an animal model that imitates the human inflammatory ocular disease by inhibiting lymphocyte proliferation. In addition, voclosporin effectively inhibited human T-cell proliferation and function in vitro. The authors report the first evidence supporting the application of voclosporin to treat intraocular inflammation.

Ocular Pathologic Features of Hermansky-Pudlak Syndrome Type 1 in an Adult

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease, characterized by a triad of oculocutaneous albinism (OCA), bleeding diathesis due to deficiency of dense bodies in platelets, and lysosomal accumulation of ceroid lipofuscin.1 Seven genetic subtypes of HPS have been identified in humans2; HPS1 on chromosome 10q23 is the most common and represents a founder effect in northwest Puerto Rico.1 The clinical features of HPS and its ophthalmic involvement3,4 are well documented, but no ocular histopathology has been published (to our knowledge). Herein, we describe the ocular histopathology of an adult patient with HPS type 1 (HPS-1).

Ocular histopathology of Ehrlichial infections in the dog.

Histologic examination of eyes and brains of 27 dogs experimentally infected with either Ehrlichia canis, E. ewingii, E. chaffeensis, or human granulocytic ehrlichia (HGE) was conducted in the course of several experiments, the primary objectives of which were to investigate the susceptibility of the domestic dog to infection with various ehrlichial species and to assess the ability of ixodid tick species to acquire and transmit those infections. Uveitis and meningitis occurred in each of the dogs infected with E. canis but was not observed in dogs infected with the other Ehrlichia species. The inflammatory infiltrate was predominantly lymphocytic, monocytic, and plasmacytic; granulocytes were notably few. Ocular inflammation was most common and most intense in the ciliary body, becoming less intense in the choroid, iris, and retina, respectively. Meningitis was often accompanied by mild neuroparenchymal vascular cuffing and gliosis. The meningeal inflammatory cell infiltrate included a prominent monocyte population. Ocular and meningeal lesions were present in all E. canis-infected dogs from 22 through 200 days postexposure. Neither ocular nor brain lesions were observed with any of the other ehrlichial infections.

Genetic mapping of a mouse ocular malformation locus, Tcm, to chromosome 4.

The Tcm mutation in the mouse is an autosomal dominant ocular malformation manifesting as microphthalmia, iris dysplasia, cataract, and coloboma. As a first step to cloning the Tcm gene, we report the localization of the Tcm mutation with respect to known microsatellite markers. Backcross progeny carrying the Tcm mutation were produced by mating Tcm/+ heterozygous mice to normal C57BL/6 partners. Genomic DNA from each mouse was subjected to PCR analysis to identify simple sequence length polymorphisms. Our results locate Tcm to Chr 4 and suggest candidate genes responsible for the Tcm phenotype. Finally, ocular histopathology was done in 3-week-old animals to define the extent of the malformation.

Tetrandrine potently inhibits herpes simplex virus type-1-induced keratitis in BALB/c mice

This study investigated the effect of tetrandrine (TDR) on ex-perimental herpes simplex keratitis (HSK) in mice. BALB/c mice were di-vided as follows: Group I, untreated; Group 2, acyclovir (ACV)-treated from day o postinfection; Group 3, ACV-treated from day 7; Group 4, TDR-treated from day O; and Group 5, TDR-treated from day 7. All mice were infected in the right cornea with herpes simplex virus (HSV) type I. TDR 30 mg/kg and ACV 120 mg/kg were administered intraperitoneally daily. The mice were observed for 14 days postinfection. Clinical inflammatory reactions and ocular histopathology were analyzed. The herpes specific antibody response and the delayed type hypersensitivity (DTH) response were stud-ied. Of the 22 untreated mice, 16 developed HSK (incidence, 72.7%). TDR given from day 7 reduced the HSK incidence to 8.5% (p< 0.01); the inci-dence of HSK was 45.4% in mice treated with TDR from day o (p >0.05). Systemic ACV given from day o inhibited HSK development (P<0.01); ACV given from day 7 resulted in an HSK incidence of 50% (p >0.05). The specific anti-HSV antibody response in the serum of mice treated with TDR or ACV either from day o or day 7 was significantly less than that of un-treated mice (p<0.01 and p<0.05, respectively), and TDR treatment sup-pressed DTH responses to HSV (p<0.05). Systemic TDR administered after HSV inoculation of the cornea significantly modulates murine HSK devel-opment at least partly by modifying the host immune/inflammatory response to the virus.

犬と猫の全身性疾患にともなう眼病変

犬と猫の全身性疾患にともなう眼病変

Ocular Pathology: A Color Atlas

This text is a revised second edition of the companion text to Ocular Pathology: A Text and Atlas by the same authors. At the time the first edition of the color atlas was released, it was a much needed addition to the pool of available ocular pathology texts. Until then no comprehensive color atlas of ocular histopathology existed, and one was desperately needed. Despite its usefulness, however, many shortcomings existed. Not least was the insufficient size of the pictures, making for poor identification of many pathologic entities. It would appear that the authors became aware of the shortcomings, leading to the development of this second edition. The organization and content of the second edition are designed to complement the recently revised third edition of the text. The new larger format makes for an even more valuable atlas. The photographs are not only larger, but in many cases the picture contrast

Ocular Histopathology: A Guide to Differential Diagnosis

In this small volume, the authors present a new and highly effective approach to the teaching of ocular histopathology. Rather than an encyclopedic compendium, they have given readers a series of diagnostic problems and have urged them to approach each diagnosis as a pathologist would. The morphologic changes are presented first. From these changes, a descriptive diagnosis is developed that can then be used as a starting point in the differential These deliberations, together with the clinical history, are used to make a final The authors have selected 52 cases, each one carefully chosen to emphasize a descriptive conclusion that they call a diagnosis. Each pivot diagnosis is used as the basis for comparison with groups of diseases that share certain morphologic features. Elements of the pivot diagnosis are described in the text and shown in accompanying photomicrographs. Differential diagnostic possibilities are listed and discussed in detail,

Ocular Histopathology. A Guide to Differential Diagnosis

Ocular Histopathology. A Guide to Differential Diagnosis

Ocular Histopathology of Vogt-Koyanagi-Harada-like Syndrome in an Akita Dog

Ocular Histopathology of Vogt-Koyanagi-Harada-like Syndrome in an Akita Dog

Epithelium-Capillary Interactions in the Eye: The Retinal Pigment Epithelium and the Choriocapillaris

Publisher Summary This chapter describes the evidence for epithelium–capillary interactions where the two are apposed, emphasizing structural and functional manifestations such as capillary permeability and cell polarity. The observations derived from human ocular histopathology and experimental animal models are focused in which interactions are evident between (1) the retinal-pigment epithelium (RPE) and its apposed capillary plexus, the choriocapillaris and (2) RPE and retinal capillaries experimentally brought into apposition with RPE, from which they are normally isolated. These observations are relevant to the pathogenesis of chorioretinal diseases like age-related macular degeneration and retinitis pigmentosa. The biology of the RPE-choriocapillaris interactions determines the relative contributions of ECM components, soluble factors, and phenotypically different types of RPE cells to observations made in situ. They are the two causes of reduced vision and blindness that arise at the RPE and lead to complicating secondary changes in the adjacent choriocapillaris and neural retina. The possible mechanisms of RPE–choriocapillaris interactions are also discussed in the chapter.

Effects of cyclosporine in spontaneous, posterior uveitis.

Cyclosporin A (CsA) was administered to chicks of the Smyth delayed-amelanotic (SDA) line from day of hatch to 4, 8 or 12 weeks of age. Animals were evaluated at 8, 12, 16 or 20 weeks with regard to major features of the SDA-line disorder, including extent of feather and choroidal amelanosis, choroidal inflammation, and histopathology of the retinal pigment epithelium and outer retina. A suppression and delay in the onset of both amelanosis and ocular histopathology occurred during CsA administration. However, a rebound enhancement of symptoms occurred 4-8 weeks after withdrawal of CsA that was closely associated with the duration of CsA treatment. These results indicate that CSA may yield therapeutic effects during the period of treatment, but its withdrawal may lead to more severe symptoms that would have occurred without treatment.

Ocular ultrastructural studies of two cases of the Hurler syndrome (systemic mucopolysaccharidosis I-H)

The ocular histopathology of Hurler syndrome (systemic mucopolysaccharidosis, type I-H), with emphasis on ultrastructural findings is reported in two cases. Numerous fine fibrillogranular inclusions were observed in: conjunctival fibrocytes; corneal epithelium, keratocytes and endothelium; uveal melanocytes and fibrocytes; ciliary epithelium; smooth muscle cells of ciliary body; pericytes; lens epithelium; retinal pigment epithelium; ganglion cells; and sclerocytes. Some multimembranous inclusions were noted in Schwann cells, keratocytes, trabecular endothelium, uveal fibrocytes and melanocytes, retinal ganglion cells, sclerocytes, optic nerve astrocytes, and vascular pericytes. Extracellular fibrillogranular material was present in the corneal stroma, Descemet's membrane, and scleral stroma. The extensive involvement of the ocular tissues of these two cases emphasizes Hurler syndrome as the most severe form of the systemic mucopolysaccharidoses.

Ocular Histopathology in Multiple Endocrine Neoplasia Type 2b

Multiple endocrine neoplasia type 2b is a syndrome, often familial, characterized by medullary carcinoma of the thyroid gland, pheochromocytoma, and many mucosal neuromas in patients who frequently have a marfanoid habitus. The ophthalmic findings are distinctive and include conjunctival and eyelid neuromas, keratoconjunctivitis sicca, and, most characteristically, greatly thickened corneal nerves. Ocular histopathologic study of a 30-year-old man demonstrated thickened nerves in the ciliary body, iris, and corneoscleral limbal regions. In these regions, the nerves were a mixture of myelinated and unmyelinated fibers. Sections through the thickened corneal nerves, 1.5 mm centrally from the corneoscleral limbus, showed only nonmyelinated nerves associated with Schwann cells. The many axons were normal in appearance but varied in diameter; some were between 0.1 and 0.2 ng and others between 1.0 and 1.4 ng. An unexpected finding was numerous ganglion cells in the ciliary body. The subconjunctival tissue showed neuromas with a minimum of fibrous structure. Sections of the lacrimal gland showed normal glandular tissue.

Ocular histopathology in animals experimentally infected with Mycobacterium leprae and M. lepraemurium. 1. Mycobacterium leprae and M. lepraemurium infections in the mouse. 2. Mycobacterium leprae infections in the 9-banded armadillo (Dasypus novemcinctus L.).

At varying periods of time following the successful establishment of systemic infections with Mycobacterium leprae or M. lepraemurium in the mouse and the nine-banded armadillo eyes were examined by light microscopy. Inoculation of bacilli was by the intravenous or intraperitoneal route or directly into the hind footpads; eyes were not directly inoculated in this study. During periods of up to 3 years under laboratory conditions no animal showed evidence of impaired vision or blindness, and the external appearance of both eyes was normal. The ocular histopathology and the sites of accumulation of bacilli are described. In immunologically normal mice infected with M. lepraemurium bacilli were much commoner in extraorbital tissues, but they were, nevertheless, found in various tissues within the orbit, including the ciliary body and sclera. In immunologically normal mice (and one rat) injected with M. leprae of human origin no bacilli were found in the eye, but in mice immunologically depressed by thymectomy and total body irradiation considerable numbers of bacilli were present in the iris and ciliary body and also in the limbal cornea. In the armadillo bacilli were found in large numbers in virtually all tissues except the lens, retina, optic nerve, and aqueous and vitreous humours, but the uveal tract was heavily involved. Findings are discussed in relation to the great frequency of ocular involvement and the importance of immune-complex disease in patients with lepromatous leprosy, and to factors wihch may favour the localisation and multiplication of Mycobacterium leprae in the eye.

Spontaneous Haemophthalmus in Leukaemia

Iris involvement in leukaemia has only rarely been described. A case of chronic myeloid leukaemia with uniocular involvement of the iris in particular, presenting with a spontaneous haemophthalmus, is reported, together with the ocular histopathology. The eye was blind due to a preceding injury.

Ocular Histopathology of Norrie's Disease

Ocular Histopathology of Norrie's Disease

The Ocular Histopathology of Homocystinuria: A Light and Electron Microscopic Study

The Ocular Histopathology of Homocystinuria: A Light and Electron Microscopic Study