SUMMARY Glaucoma is the leading cause of irreversible blindness and is characterized by the death of retinal ganglion cells (RGCs). Recent studies have implicated pro-inflammatory microglia, macrophages, and A1 astrocytes in the pathogenesis of neurodegenerative diseases. The role of pro-inflammatory, neurotoxic A1 astrocytes in glaucoma is just beginning to be explored. Using a mouse model of glaucoma, we demonstrate that ocular hypertension is sufficient to trigger production of C1q, interleukin-1α (IL-1α), and tumor necrosis factor α (TNF-α), three cytokines necessary and sufficient to drive the formation of A1 astrocytes. Upregulation of these cytokines occurs first in CD11b + CD11c + cells followed by CD11b + CD11c − cells. Ablation of this pathway, by either genetic deletions of C1qa, IL-1α, and TNF-α, or treatment with glucagon-like peptide-1 receptor agonist NLY01, reduces A1 astrocyte transformation and RGC death. Together, these results highlight a neuroinflammatory mechanism of glaucomatous neurodegeneration that can be therapeutically targeted by NLY01 administration.

Vision and audition represent the outside world in spatial synergy that is crucial for guiding natural activities. Input conveying eye-in-head position is needed to maintain spatial congruence because the eyes move in the head while the ears remain head-fixed. Recently, we reported that the human perception of auditory space shifts with changes in eye position. In this study, we examined whether this phenomenon is 1) dependent on a visual fixation reference, 2) selective for frequency bands (high-pass and low-pass noise) related to specific auditory spatial channels, 3) matched by a shift in the perceived straight-ahead (PSA), and 4) accompanied by a spatial shift for visual and/or bimodal (visual and auditory) targets. Subjects were tested in a dark echo-attenuated chamber with their heads fixed facing a cylindrical screen, behind which a mobile speaker/LED presented targets across the frontal field. Subjects fixated alternating reference spots (0, +/-20 degrees ) horizontally or vertically while either localizing targets or indicating PSA using a laser pointer. Results showed that the spatial shift induced by ocular eccentricity is 1) preserved for auditory targets without a visual fixation reference, 2) generalized for all frequency bands, and thus all auditory spatial channels, 3) paralleled by a shift in PSA, and 4) restricted to auditory space. Findings are consistent with a set-point control strategy by which eye position governs multimodal spatial alignment. The phenomenon is robust for auditory space and egocentric perception, and highlights the importance of controlling for eye position in the examination of spatial perception and behavior.

The purpose of this study was to investigate the association between gender and primary open-angle glaucoma (POAG) among African Americans and to assess demographic, systemic, and behavioral factors that may contribute to differences between genders. The Primary Open-Angle African American Glaucoma Genetics (POAAGG) study had a case-control design and included African Americans 35 years and older, recruited from the greater Philadelphia, Pennsylvania. Diagnosis of POAG was based on evidence of both glaucomatous optic nerve damage and characteristic visual field loss. Demographic and behavioral information, history of systemic diseases and anthropometric measurements were obtained at study enrollment. Gender differences in risk of POAG were examined using multivariate logistic regression. A total of 2,290 POAG cases and 2,538 controls were included in the study. The percentage of men among cases was higher than among controls (38.6% vs 30.3%, P<0.001). The subjects’ mean age at enrollment was significantly higher for cases compared to controls (70.2±11.3 vs. 61.6±11.8 years, P<0.003). Cases had lower rates of diabetes (40% vs. 46%, P<0.001), higher rates of systemic hypertension (80% vs. 72%, P<0.001), and lower body mass index (BMI) (29.7±6.7 vs. 31.9±7.4, P<0.001) than controls. In the final multivariable model, male gender was significantly associated with POAG risk (OR, 1.64; 95% CI, 1.44–1.87; P<0.001), after adjusting for age, systemic hypertension, diabetes, and BMI. Within the POAAGG study, men were at higher risk of having POAG than women. Pending genetic results from this study will be used to better understand the underlying genetic variations that may account for these differences.

Exclusion of the contralateral eye tissue when there was difficulty in graft peeling for the first eye may prove to be a unique quality of DMEK donor tissue.