Loss of corneal sensory nerve fibers in SIV-infected macaques: an alternate approach to investigate HIV-induced PNS damage.
Peripheral neuropathy is the most frequent neurological complication of HIV infection, affecting more than one-third of infected patients, including patients treated with antiretroviral therapy. Although emerging noninvasive techniques for corneal nerve assessments are increasingly being used to diagnose and monitor peripheral neuropathies, corneal nerve alterations have not been characterized in HIV. Here, to determine whether SIV infection leads to corneal nerve fiber loss, we immunostained corneas for the nerve fiber marker βIII tubulin. We developed and applied both manual and automated methods to measure nerves in the corneal subbasal plexus. These counting methods independently indicated significantly lower subbasal corneal nerve fiber density among SIV-infected animals that rapidly progressed to AIDS compared with slow progressors. Concomitant with decreased corneal nerve fiber density, rapid progressors had increased levels of SIV RNA and CD68-positive macrophages and expression of glial fibrillary acidic protein by glial satellite cells in the trigeminal ganglia, the location of the neuronal cell bodies of corneal sensory nerve fibers. In addition, corneal nerve fiber density was directly correlated with epidermal nerve fiber length. These findings indicate that corneal nerve assessment has great potential to diagnose and monitor HIV-induced peripheral neuropathy and to set the stage for introducing noninvasive techniques to measure corneal nerve fiber density in HIV clinical settings.
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Jamie L
JL
Dorsey
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Lisa M
LM
Mangus
Voxeleron, Pleasanton, California.
Jonathan D
JD
Oakley
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Sarah E
SE
Beck
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Kathleen M
KM
Kelly
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Suzanne E
SE
Queen
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Kelly A
KA
Metcalf Pate
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Robert J
RJ
Adams
Department of Anatomy and Cell Biology, Indiana University School of Medicine-Northwest, Gary, Indiana.
Carl F
CF
Marfurt
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: jmankows@jhmi.edu.
Joseph L
JL
Mankowski
D000818:Animals; D003315:Cornea / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D004817:Epidermis / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism / Q000517:prevention & control; D015497:HIV-1; D008254:Macaca nemestrina; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism / Q000473:pathology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism / Q000473:pathology; D015302:Simian Immunodeficiency Virus
D005904:Glial Fibrillary Acidic Protein