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M. Singh, A. Shariati, F. N. Ross-Cisneros, W. R. Freeman, A. A. Sadun; An Immunohistochemical (IHC) Examination of Role of N-Methyl D- Aspartate (NMDA) Receptor as a Mediator of Damage in Optic Nerves of Patients with Chronic HIV Infection. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5346.
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To determine if activation of NMDA receptors plays a role in the damage of optic nerves of the patients chronically infected with HIV.
28 retro bulbar optic nerves were collected at autopsy from 14 patients previously established to have chronic HIV infection. Six age matched control retro bulbar optic nerves were also collected. The nerves were immersion-fixed in 10% formalin. 3mm cross-sections of the nerves were embedded into paraffin and then cut on a microtome at 4microns. A two step indirect IHC staining method was employed using an HRP-conjugated secondary antibody reacting with a DAB substrate-chromogen system. The Primary antibody directed against human NMDA was diluted to 1:20. The slides were analyzed using a Zeiss Axioskop light microscope. The optic nerve’s IHC staining was graded on a scale from 0 to 4. 0 staining appeared to have none, or very trace evidence of DAB+ staining within the optic nerve tissue and the surrounding dura. A 4 appeared to have specific , heavy staining throughout the optic nerve.
We examined 38 nerves from 14 HIV patients. 4 of the 28 patients had a Grade 4 positive staining. Positive staining of NMDA was found in the neural tissue of HIV nerves as well as the control nerves, but the density of the staining was found to be more in the HIV nerves than in the negative control nerves. The density of NMDA receptors as evidenced by staining shows a continuum from being more dense to a decreasing density as the apoptotic process continues and neural tissue drop out occurs. These nerves ultimately show degeneration.
The optic nerves of HIV positive patients have an up regulation of NMDA receptors which leads to excitotoxic injury to these nerves leading to cell loss and degeneration. This study shows the evidence of optic nerve damage in HIV positive patients as a result of NMDA receptor activation by the viral proteins.
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