Background Coronavirus 2019 disease (COVID-19) is caused by the virus SARS-CoV-2, transmissible both person-to-person and from contaminated surfaces. Early COVID-19 detection among healthcare workers (HCWs) is crucial for protecting patients and the healthcare workforce. Because of limited testing capacity, symptom-based screening may prioritize testing and increase diagnostic accuracy.

Although the molecular pathophysiology of diabetic retinopathy, the current leading cause of blindness in Western societies, 1 is not fully elucidated, studies have documented a pivotal role for leukocyte adherence within the retinal vasculature. The adhesion of leukocytes to the retinal endothelium is a process that depends on ␤ 2 integrin-intercellular adhesion molecule (ICAM)-1 interactions and leads to breakdown of the blood-retinal barrier. 2 These data, in combination with our previous findings that aggressive anti-inflammatory therapy suppressed leukocyte adhesion and blood retinal breakdown in a relevant animal model, 3 support the hypothesis that a chronic subclinical inflammation may underlie much of the vascular pathology of diabetic retinopathy. 4 These vascular pathological findings are orchestrated by vascular endothelial growth factor (VEGF), a factor that potently promotes the growth and maintenance of endothelial cells and the formation of new vessels, and is implicated in both background and proliferative diabetic retinopathy. 5-11 Intraocular VEGF levels are increased in diabetic patients with blood-retinal barrier breakdown and neovascularization, 5,10,12,13 whereas the specific inhibition of VEGF prevents these complications in animal models. 7,11,14 Therefore, regulation of VEGF expression could conceivably be both a mediator for converging local and systemic stimuli modulating vessel pathophysiology, as well as a target for therapeutic intervention. Within a constellation of known modulators of VEGF expression that can possibly function at the transcriptional [through AP-1, AP-2, steroid hormone receptors, p53, and nuclear factor (NF-B)] or posttranscriptional level, [15][16][17][18] hypoxia is the most potent inducer of VEGF transcription in vivo; its effects are mainly mediated by the helix-loop helix (bHLH)-PAS transcription factor HIF-1␣, which heterodimerizes with the bHLH-PAS protein ARNT or HIF-1␤, 19 -22 and binds to consensus and ancillary hypoxia-response elements (HREs) in the VEGF promoter. 21,[23][24][25]

Heat shock protein (Hsp) 90 inhibitors, such as 17-allylamino-17-demethoxy-geldanamycin (17-AAG), constitute promising novel therapeutic agents. We investigated the anti-inflammatory activity of 17-AAG in endotoxin-induced uveitis (EIU) in rats. After the induction of EIU with a footpad injection of lipopolysaccharide (LPS), female Lewis rats received a single intraperitoneal. (i.p.) injection of 17-AAG or vehicle. Twenty-four hours later, the retinas were extracted and assayed for leukocyte adhesion; blood-retinal barrier breakdown; VEGF, TNF-alpha, IL-1beta, and CD14 protein levels; NF-kappaB and HIF-1alpha activity; hsp90 and 70 levels and expression and phosphorylation of the tight junction proteins ZO-1 and occludin. 17-AAG treatment significantly suppressed the LPS-induced increase in retinal leukocyte adhesion; vascular leakage; NF-kappaB, HIF-1alpha, p38, and PI-3K activity; and VEGF, TNF-alpha, and IL-1beta levels. 17-AAG also suppressed phosphorylation of ZO-1 and occludin by inhibiting their association with p38 and PI-3K. Although 17-AAG treatment did not reduce the LPS-induced increase in total CD14 levels in leukocytes, it significantly decreased membrane CD14 levels. These data suggest that Hsp90 inhibition suppresses several cardinal manifestations of endotoxin-induced uveitis in the rat. 17-AAG has demonstrated a favorable safety profile in clinical trials in cancer patients and represents a promising therapeutic agent for the treatment of inflammatory eye diseases.