Baylor College of Medicine 1978
Molecular Genetics and Biochemistry
Cellular, Molecular Biology and Physiology
Molecular Genetics / Neuro-Biology, Ocular Virology and Immunology
Molecular Genetics/Neurobiology, Ocular Virology and Immunology
The eye is an immune-privileged site of the body that possesses a number of structural barriers and immunologic strategies to preserve vision. Despite these novel barriers and strategies, viruses use a variety of unique pathogenic mechanisms to invade retinal tissues and establish infection, a process that often leads to destruction of the delicate structural architecture of the retina (retinitis) and ultimately vision loss and blindness.
My research program through funding by the National Eye Institute of the National Institutes of Health focuses on understanding the key events that take place during onset and development of retinal diseases caused by human herpesviruses, especially human cytomegalovirus (HCMV). This human herpesvirus is responsible for a sight-threatening retinitis in persons who are immunosuppressed, including persons with AIDS. These investigations are being pursued using a clinically relevant animal model of mouse cytomegalovirus (MCMV) retinitis unique to my laboratory that employs mice with a retrovirus-induced immunosuppression (MAIDS), a mouse model that mimics HIV-induced immunosuppression during AIDS. Previous work from my laboratory using the MAIDS model of MCMV retinitis have investigated the precise roles of antibody and cellular immunity in protection against development of HCMV retinitis in immunologically normal persons. More recent work has explored immune proteins known as cytokines to determine their potential contributions to retinal tissue destruction during evolution of MAIDS-related MCMV retinitis. Present investigations are underway to determine with greater precision how different cell death pathways such as apoptosis, necroptosis, and pyroptosis may conspire with virus-induced cell death to cause the severe retinal cell destruction associated with retinitis.
My laboratory has recently expanded its interests in diseases of the eye to include age-related macular degeneration (AMD), the leading cause of severe irreversible central vision loss and legal blindness in the growing elderly population. The neovascular “wet” form of AMD develops through formation of new blood vessels within the macula of the retina which physically disrupts its structural architecture and thereby leads to loss of sight. Cofactors previously identified for development of wet AMD include smoking of nicotine, high-fat diet, and genetics. In collaboration with an ocular immunology research group at Duke University, we have used a mouse model of neovascular AMD to provide new evidence that chronic cytomegalovirus infection of circulating monocytes in the blood may serve as yet another key cofactor in development of wet AMD.
Collectively, these investigations are designed to lead to new paradigms of disease pathogenesis for better diagnosis and management of AIDS-related HCMV retinitis and wet AMD in the clinical setting.
Cousins SW, Espinosa-Heidmann DG, Miller DM Pereira-Simon S, Hernandez EP, Chien H, Meier-Jewett C, Dix RD (2012) Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization. PLoS Pathogens 8(4): e1002671. doi:10.1371/Journalppat.1002671
Chien H, Dix RD (2012) Evidence for multiple cell death pathways during development of experimental cytomegalovirus retinitis in mice with retrovirus-induced immunosuppression: apoptosis, necroptosis, and pyroptosis. J Virol 86(20): 10961-10978. doi:10.1128/JVI.01275-12.
Alston CI, Dix RD (2017) Murine cytomegalovirus infection of mouse macrophages stimulates early expression of suppressor of cytokine signaling (SOCS1) and SOCS3. PLoS One 12(2): e0171812. Doi10.1371/journal.pone.0171812
Alston CI, Dix RD (2017) Reduced frequency of murine cytomegalovirus retinitis in C57BL/6 mice correlates with low levels of suppressor of cytokine signaling (SOCS)1 and SOCS3 expression within the eye during corticosteroid-induced immunosuppression. Cytokine 97: 38-41.