Contralateral Astrocyte Response to Acute Optic Nerve Damage Is Mitigated by PANX1 Channel Activity.

Glial reactivity is considered a hallmark of damage-induced innate immune responses in the central nervous system. In the visual system, unilateral optic nerve damage elicits dramatic glial reactivity in the retina directly affected by the lesion and a similar, albeit more modest, effect in the contralateral eye. Evaluation of astrocyte changes in a mouse model of optic nerve crush indicates that astrocyte reactivity, as a function of retinal coverage and cellular hypertrophy, occurs within both the experimental and contralateral retinas, although the hypertrophic response of the astrocytes in the contralateral eyes is delayed for at least 24 h.

Retinal glial responses to optic nerve crush are attenuated in Bax-deficient mice and modulated by purinergic signaling pathways.

Background: Retinal ganglion cell (RGC) soma death is a consequence of optic nerve damage, including in optic neuropathies like glaucoma. The activation of the innate immune network in the retina after nerve damage has been linked to RGC pathology. Since the eye is immune privileged, innate immune functions are the responsibility of the glia, specifically the microglia, astrocytes, and Müller cells that populate the retina.

Neuroinflammation in Glaucoma and Optic Nerve Damage.

Glaucoma is a group of optic neuropathies characterized by the degeneration of retinal ganglion cell axons and somas, ultimately preventing light signals in the retina from reaching the brain. Glaucoma is a leading cause of blindness in the world, and treatment options for patients remain limited and minimally efficacious. A number of mechanisms have been linked to glaucomatous pathophysiology.

Tumor necrosis factor alpha has an early protective effect on retinal ganglion cells after optic nerve crush.

Background: Glaucoma is an optic neuropathy that is characterized by the loss of retinal ganglion cells (RGCs) initiated by damage to axons in the optic nerve. The degeneration and death of RGCs has been thought to occur in two waves. The first is axogenic, caused by direct insult to the axon.

Evaluation of the percentage of ganglion cells in the ganglion cell layer of the rodent retina.

Purpose: Retinal ganglion cells comprise a percentage of the neurons actually residing in the ganglion cell layer (GCL) of the rodent retina. This estimate is useful to extrapolate ganglion cell loss in models of optic nerve disease, but the values reported in the literature are highly variable depending on the methods used to obtain them.

Methods: We tested three retrograde labeling methods and two immunostaining methods to calculate ganglion cell number in the mouse retina (C57BL/6).

Adoptive transfer of lymphocytes isolated from simian immunodeficiency virus SIVmac239Δnef-vaccinated macaques does not affect acute-phase viral loads but may reduce chronic-phase viral loads in major histocompatibility complex-matched recipients.

The live attenuated simian immunodeficiency virus (SIV) SIVmac239Δnef is the most effective SIV/human immunodeficiency virus (HIV) vaccine in preclinical testing. An understanding of the mechanisms responsible for protection may provide important insights for the development of HIV vaccines. Leveraging the uniquely restricted genetic diversity of Mauritian cynomolgus macaques, we performed adoptive transfers between major histocompatibility complex (MHC)-matched animals to assess the role of cellular immunity in SIVmac239Δnef protection.

Nuclear atrophy of retinal ganglion cells precedes the bax-dependent stage of apoptosis.

Purpose: Retinal ganglion cells atrophy during the execution of the intrinsic apoptotic program. This process, which has been termed the apoptotic volume decrease (AVD) in other cell types, has not been well-characterized in ganglion cells.

Methods: Acute optic nerve crush was used to examine neuronal atrophy in the ganglion cell layer in wild-type and Bax-deficient mice.

High viremia is associated with high levels of in vivo major histocompatibility complex class I Downregulation in rhesus macaques infected with simian immunodeficiency virus SIVmac239.

Human and simian immunodeficiency viruses (HIV and SIV) downregulate major histocompatibility complex class I (MHC-I) molecules from the surface of infected cells. Although this activity is conserved across viral isolates, its importance in AIDS pathogenesis is not clear. We therefore developed an assay to detect the level of MHC-I expression of SIV-infected cells directly ex vivo.

Infection with "escaped" virus variants impairs control of simian immunodeficiency virus SIVmac239 replication in Mamu-B*08-positive macaques.

An understanding of the mechanism(s) by which some individuals spontaneously control human immunodeficiency virus (HIV)/simian immunodeficiency virus replication may aid vaccine design. Approximately 50% of Indian rhesus macaques that express the major histocompatibility complex (MHC) class I allele Mamu-B*08 become elite controllers after infection with simian immunodeficiency virus SIVmac239. Mamu-B*08 has a binding motif that is very similar to that of HLA-B27, a human MHC class I allele associated with the elite control of HIV, suggesting that SIVmac239-infected Mamu-B*08-positive (Mamu-B*08+) animals may be a good model for the elite control of HIV.

Vaccine-induced cellular responses control simian immunodeficiency virus replication after heterologous challenge.

All human immunodeficiency virus (HIV) vaccine efficacy trials to date have ended in failure. Structural features of the Env glycoprotein and its enormous variability have frustrated efforts to induce broadly reactive neutralizing antibodies. To explore the extent to which vaccine-induced cellular immune responses, in the absence of neutralizing antibodies, can control replication of a heterologous, mucosal viral challenge, we vaccinated eight macaques with a DNA/Ad5 regimen expressing all of the proteins of SIVmac239 except Env.