BIOL 4576 Exam # 5 Study Guide Lectures: 16-19Lecture 16 Ocular Virology-Retina- Anterior and posterior segment of the eye- 2 vasculatures in the eyeo One of them nearer the top have tight junctions but no astrocyteso The choroid vasculature is fenestrated but the blood passes through tight junctions in the basement membrane.- Only parts of the eye are immune privileged o Intraocular compartments and tissues are, blood ocular barrierso Ocular surface (cornea and conjunctiva) are part of the mucosal immune system- There is local antibody synthesis in the eye. Goldmann-Witmer coefficient compares intraocular fluid to serum ratio of viral Ig to intraocular fluid to serum ratio of total Ig. OCGs can be found in aqueous humor.ACAID (Anterior Chamber Associated Immune Deviation)- Systemic immune deviation that occurs soon after placement of foreign antigen into the anterior chamber of the eye of a healthy animal- Injection of antigen causes macrophages to act as APCs. Cytokines in the aqueous humorcreate immunosuppressive environment in the eye. TGFbeta, alphaMSH, and VIP are secreted. APCs that have the antigen exit the eye and enter circulation where they travelto the spleen. T suppressor cells inhibit DTH response and there are no complement antibodies. Inflammation can’t be mobilized. This is not a global immunodeficiency. There is normal innate, CD8, and other antibodies.Herpes Simplex Retinitis- This occurs around the same time that herpes simplex encephalitis occurs in immunologically normal patients. HSV1 causes this bilateral disease.- Inflammation of the optic nerve, pigmented epithelium, and retina (no ant segment)- Inclusion bodies and herpesvirus particles are in these places, HSV1 DNA in vitreous humor- Degree of inflammation, retinal necrosis, and hemorrhage can varyAcute Retinal Necrosis- Occurs bilaterally in most cases of immunologically normal people around the age of 60- Mostly caused by VZV, usually occurs around time of VZV infection- Symptoms: ocular discomfort, photophobia, floaters, redness, elevated ocular pressureo Progresses to retinal necrosis, occlusive vasculitis, vitritis, retinal detachment- Lasts 3 weeks but causes vision loss- Virus can come from reactivation or from primary infection (hematogenous route)- Pathogenesiso Viremia: retinal arteriolar walls infectedo Inflammation causes breakdown of BRB/BOB, immune complexes cause occlusivevasculitiso Retinal necrosis: direct infection, inflammation, ischemia (no O2), schesis- Caused by HSV1 and HSV2- Mouse model: von szily: inoculate eye with HSV1 and retinal necrosis occurs in other eye(spreads through optic nerve) (due to ACAID?)- Treatment: acyclovir (doesn’t affect retinal detachment), corticosteroids for inflammation, anticoagulants, surgical repair of retina- Visual acuity loss depends on severity- B virus could be related.AIDS related cytomegalovirus retinitis- This HHV beta virus affects around 80% of people and it usually is asymptomatic in immunologically normal people. It is shed in urine and saliva. The virus is cleared but then goes latent inside macrophages. - It can be an opportunistic infection in immunocompromised patients. Examples are patients with organ or bone marrow allografts or HIV. Patients with allografts usually develop pneumonitis. Patients with AIDS usually develop retinitis.- It is slow progressive focal or multifocal necrotizing retinitis.- Symptoms: floaters and loss of visual acuity, retinal lesions (due to viral infection), hemorrhage, retinal detachment, vision loss and blindness, moves to other eye- Histopathology: retinal necrosis, transition zones, cytomegalic cells, viral inclusions, inflammatory cells, hemorrhage- Treatment: ganciclovir, foscarnet, cidofovir, cART (prevents HIV immunosuppression)Uveitis- EAU in rats resembles clinical uveitis which causes vision loss and blindness- Induced by retinal proteins and CFA- CD4 Tcells destroy photoreceptors cells and CD8 cells destroy retina- CNS vs Eye is important to know probably.Lecture 17 Ocular Virology-CorneaEpidemic Keratoconjunctivitis (pink eye)- Caused by adenoviruso 7 subgroups, over 57 serotypes (differ in infection site and age) 6 associated with pink eye: 3,4,7,8,19,37 (mostly 8,19,37)- Symptoms: due to replication of adenovirus and inflammation: tearing, redness, foreign body sensation, photophobia, lid swelling, vision disturbanceso Foreign body sensation due to diffuse punctate keratitis that coalesce o Bilateral: one eye then the othero Virus recovered from ocular surfaceo Resolves in a few weekso No treatment (no antivirals), corticosteroids, cold compresseso Most people keep vision but 3% have vision lossHerpes Simplex Keratitis- HSV1 is cause and most common infectious cause of blindness- 3 forms: dendritic and stromal (disciform and herpes stromal)- Dendritic: macroscopic lesions due to viral infection, usually healo Small lesions merge to form dendrites and then geographic ulcers- Disciform: corneal edemao 2 theories:  corneal epithelium dysfunction leads to stromal edema DTH to HSV1 antigens leads to stromal edema- Herpes Stromal Keratitiso Necrotizing keratitis which causes scarring and loss of visiono No infectious virus detectedo Immunopathologic disease because antigens remain in eyeo Pannus formation, fragmentation of bowman membrane, scarring, stromal necrosiso Mouse model: mouse eye inoculated with HSV1 on the cornea. Dendrites develop quickly. Replicating virus clears quickly.  Neutrophils go to cornea (innate). Cytokines are released.  Virus goes quiescent but then after infection, neovascularization occurs on the cornea, leukocytes invade This progresses to severe necrotizing keratitis, stromal inflammation, and epithelial necrosis. CD4 t cells and Tregs and CD8 t cells moderate this diseaseo Treatment: topical corticosteroids and topical antivirals Corneal allografts, can happen at each reactivation- HSV2 corneal diseaseo It’s rare. When it does occur, it is usually in neonates. o Causes corneal ulceration, anterior uveitis, cataract formation- Acute Hemorrhagic Conjunctivitis o Caused by enterovirus 70 and coxsackie virus A24o Transmitted fecal-orally by fomites or contaminated fingerso Short incubation: severe ocular pain, lid swelling, tearing, redness, photophobia, foreign body sensation, and blurry visiono Both eyes, one shortly after the othero Symptoms resolve in a