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HIV-1 Tat-Mediated Neurotoxicity in Retinal Cells

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Abstract

The current study was aimed at investigating the effect of HIV-1 protein Tat on the retinal neurosensory cell line R28. Exposure of Tat resulted in induction of pro-inflammatory mediators such as CXCL10 and TNF-α in addition to the activation marker GFAP in these cells. Conditioned media from Tat-treated R28 cells was able to induce monocyte migration, an effect that was blocked by CXCR3 antagonist. Complementary studies in the HIV-1 Tat-transgenic mice, showed a complete absence of the nuclear layer and the outer photoreceptor segments of the retina with a concomitant increase in glial activation. These findings lend support to the observation in post-HAART era of increased incidence of immune response-mediated retinal degeneration. These findings have direct relevance to diseases such as immune response uveitis and patients recovering from CMV retinitis.

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Acknowledgments

The authors thank Dr. Sabita Roy, University of Minnesota for providing the HIV-1 Tat-transgenic mice eyeballs. The authors also thank the Confocal Laser Scanning Microscope Core Facility at the University of Nebraska Medical Center for providing assistance with confocal microscopy and the Nebraska Research Initiative and the Eppley Cancer Center for their support of the Core Facility. We thank Dr. Sitabhra Sinha for his help in generating Fig. 2 with MATLAB. NC was supported by the Indian Council of Medical Research Young Biomedical Scientist Fellowship while working at UNMC on this work. GMS is supported by R21CA127061, a departmental challenge grant from Research to Prevent Blindness and a Vision Research core infrastructure grant 1R24EY016662 and by U54CA143876 from the National Cancer Institute.

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Nivedita Chatterjee, Shilpa J. Buch

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Authors and Affiliations

  1. Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, 41 College Road, Chennai, 600006, India

    Nivedita Chatterjee

  2. Center for Hearing and Deafness, University at Buffalo, 3435 Main Street, Cary 137, Buffalo, NY, 14214, USA

    Gail M. Seigel

  3. Department of Pharmacology and Experimental Neuroscience, Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA

    Shannon Callen & Shilpa J. Buch

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  1. Nivedita Chatterjee
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Correspondence to Nivedita Chatterjee.

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Chatterjee, N., Callen, S., Seigel, G.M. et al. HIV-1 Tat-Mediated Neurotoxicity in Retinal Cells. J Neuroimmune Pharmacol 6, 399–408 (2011). https://doi.org/10.1007/s11481-011-9257-8

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