BIOL 4576 Exam 5 Study Guide Lectures 16 19 Lecture 16 Ocular Virology Retina Anterior and posterior segment of the eye 2 vasculatures in the eye o One of them nearer the top have tight junctions but no astrocytes o 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 barriers o 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 humor create immunosuppressive environment in the eye TGFbeta alphaMSH and VIP are secreted APCs that have the antigen exit the eye and enter circulation where they travel to 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 vary Acute 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 pressure o 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 Pathogenesis o Viremia retinal arteriolar walls infected o Inflammation causes breakdown of BRB BOB immune complexes cause occlusive vasculitis o 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 Cornea Epidemic Keratoconjunctivitis pink eye Caused by adenovirus o 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 disturbances o Foreign body sensation due to diffuse punctate keratitis that coalesce o Bilateral one eye then the other o Virus recovered from ocular surface o Resolves in a few weeks o No treatment no antivirals corticosteroids cold compresses o Most people keep vision but 3 have vision loss Herpes 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 heal o Small lesions merge to form dendrites and then geographic ulcers Disciform corneal edema o 2 theories corneal epithelium dysfunction leads to stromal edema DTH to HSV1 antigens leads to stromal edema Herpes Stromal Keratitis o Necrotizing keratitis which causes scarring and loss of vision o No infectious virus detected o Immunopathologic disease because antigens remain in eye o Pannus formation fragmentation of bowman membrane scarring stromal necrosis o 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 disease o Treatment topical corticosteroids and topical antivirals Corneal allografts can happen at each reactivation HSV2 corneal disease o 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 A24 o Transmitted fecal orally by fomites or contaminated fingers o Short incubation severe ocular pain lid swelling tearing redness photophobia foreign body sensation and blurry vision o Both eyes one shortly after the other o Symptoms resolve in a few days o Hemorrhages small petechiae to large blotches o No treatment only cold compresses Lecture 18 Alzheimer s Disease This is the most common neurological disease that results in a progressive and age related dementia Mild Alzheimer s Gradual onset including memory