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.

The phosphorylation of eukaryotic initiation factor 2 (p-eIF2) during dietary amino acid insufficiency reduces protein synthesis and alters gene expression via the integrated stress response (ISR). We explored whether a Met-restricted (MR) diet activates the ISR to reduce body fat and regulate protein balance. Male and female mice aged 3-6 mo with either whole-body deletion of general control nonderepressible 2 () or liver-specific deletion of protein kinase R-like endoplasmic reticulum kinase () alongside wild-type or floxed control mice were fed an obesogenic diet sufficient in Met (0.86%) or an MR (0.12% Met) diet for ≤5 wk. Ala enrichment with deuterium was measured to calculate protein synthesis rates. The guanine nucleotide exchange factor activity of eIF2B was measured alongside p-eIF2 and hepatic mRNA expression levels at 2 d and 5 wk. Metabolic phenotyping was conducted at 4 wk, and body composition was measured throughout. Results were evaluated with the use of ANOVA ( < 0.05). Feeding an MR diet for 2 d did not increase hepatic p-eIF2 or reduce eIF2B activity in wild-type or mice, yet many genes transcriptionally regulated by the ISR were altered in both strains in the same direction and amplitude. Feeding an MR diet for 5 wk increased p-eIF2 and reduced eIF2B activity in wild-type but not mice, yet ISR-regulated genes altered in both strains similarly. Furthermore, the MR diet reduced mixed and cytosolic but not mitochondrial protein synthesis in both the liver and skeletal muscle regardless of status. Despite the similarities between strains, the MR diet did not increase energy expenditure or reduce body fat in mice. Finally, feeding the MR diet to mice with deleted in the liver increased hepatic p-eIF2 and altered body composition similar to floxed controls. Hepatic activation of the ISR resulting from an MR diet does not require p-eIF2. status influences body fat loss but not protein balance when Met is restricted.

Many factors influence an applicant's matriculation into an ophthalmology residency program. Previous studies have assessed the importance of quantifiable aspects of the application, such as board scores, Alpha Omega Alpha (AOA) status, and clinical grades in matching into ophthalmology. 1,2Although research was mentioned in several of these studies, its effects on the match process has never been quantified. A survey of program directors, chairpersons, and people involved in matching committees indicated that a year of research was noted to be helpful in improving ophthalmology applications. 3In this study, we analyze the correlation between different research parameters and the rank of residency program matched, as measured by research output and reputation. Similar bibliometric studies have been done to evaluate the impact of research on matching into neurosurgery.4 An objective analysis of the often-elusive term "research" can help medical students and advisors understand the impact of AbstractPurpose This article aims to quantify the impact of research on matching into various tiers of ophthalmology residency programs. Design In this study, 340 applicants who matriculated into ophthalmology residency programs in the United States from the class of 2019 were included. Data variables collected for each applicant composed of the following: Hirsch's index (h-index), total number of publications, journal impact factor, type of publication, and number of publications relating to ophthalmology. The primary outcome was tier of ophthalmology program that each applicant matched into, which was determined by two metrics:(1) the h-index of the department's faculty and (2) overall reputation of the residency program as characterized by the U.S. News and World Report Ophthalmology Rankings. Results After multivariate analysis, only the h-index was found to be associated with an increased likelihood of matching at a higher tier program when measuring tier based on the metric of institutional research output (p < 0.0001). However, no research variable was found to be significant on multivariate analysis when assessing the impact of research on matching into a certain tier program based on reputation. The h-index was noted to increase by 1 for every 3.1 papers as the first author, every 4.9 years since the first publication, every 6.4 ophthalmology-related publications, and every publication in a journal with an impact factor of 5.2. Conclusion A higher applicant h-index is associated with matching at an ophthalmology program with greater research output; however, it is not associated with reputation of residency program.

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