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Creation of RD caused a dramatic increase of HMGB1 protein IF in rods. cKO of HMGB1 in rods did not affect retinal structure or function. However, after RD, loss of rods and reduction in the thickness of the outer nuclear layer were significantly increased in the HMGB1ΔRod retinas as compared to the control. Interestingly, depletion of HMGB1 in rods did not affect the activation and mobilization of microglia/macrophages normally seen after RD. Conclusions Increased HMGB1 expression in stressed rods may represent an intrinsic mechanism regulating their survival after RD.Purpose The purpose of this study was to determine if treatment with telmisartan, an angiotensin II type 1 receptor blocker (ARB), protects against retinal ganglion cell (RGC) degeneration in a mouse glaucoma model with induced elevation of intraocular pressure (IOP). Methods IOP elevation was induced by injection of polystyrene microbeads into the anterior chamber of the right eye of 3-month-old C57BL/6J mice, with the left eye serving as contralateral control. Starting the day of microbead injection, mice were maintained on solid food pellets with or without incorporated telmisartan. IOP was measured by Tono Lab tonometry prior to and weekly after microbead injection. Twelve weeks postinjection, mice were euthanized to obtain optic nerves for analysis of RGC axons. The total numbers of optic nerve axons were determined manually and automatedly using AxonJ. Degenerating axons were counted manually. Results IOP elevation induced by microbead injection was similar in magnitude and duration in vehicle and telmisartan-fed mice, although IOP was reduced 5.8% in uninjected mice treated with telmisartan (P = 0.0027). Axon loss determined by manual and automated methods was greater in vehicle compared to telmisartan-treated mice (manual 9.5% vs. 1.8%, P = 0.044; automated 14.2% vs. 2.9%, P = 0.0375). An increase in the percent of axons undergoing degeneration was observed in nerves from microbead-injected eyes that was greater in vehicle-treated compared to telmisartan-treated mice (49.0% vs. -0.58%, P = 0.0019). Conclusions Elevation of IOP by microbead injection led to loss of RGC axons in vehicle-treated mice that was largely prevented by telmisartan treatment, suggesting a neuroprotective effect of telmisartan.Purpose Ultraviolet radiation from sunlight contributes to age-related cataract and skin cancer. The EPHA2 gene is implicated in both these diseases. The purpose of this study was to determine whether age-related cataract and skin cancer are associated in a cohort of older Australians. Methods A cross-sectional study was performed using the Historical Cohort of the Registry of Senior Australians. Individuals aged ≥65 years or aged ≥50 years and of Aboriginal or Torres Strait Islander descent, who had an aged care eligibility assessment between July 2005 and June 2015, and had a history of cataract surgery and/or skin cancer according to the Australian Government Medicare Benefits Schedule dataset, during the 3-year period prior, were evaluated (N = 599,316). A multivariable logistic regression model was used to determine association and multiple hypothesis correction was employed. Results Of the evaluated individuals, 87,097 (14.5%) had a history of cataract and 170,251 (28.4%) a history of skin cancer. Among those with a history of cataract, 20,497 (23.5%), 1127 (1.3%), and 14,730 (16.9%) individuals had a concurrent history of keratinocyte, melanoma, and premalignant/solar keratosis, respectively. Those with a history of cataract were 19% more likely to have a history of skin cancer (odds ratio [OR], 1.19; 95% confidence interval [CI], (1.17-1.21). Co-occurrence of keratinocyte skin cancer was 16% (OR, 1.16; 95% CI, 1.14-1.18), melanoma 21% (OR, 1.21; 95% CI, 1.13-1.29), and premalignant/solar keratosis 19% (OR, 1.19; 95% CI, 1.17-1.22) more in the presence than absence of history of cataract. Conclusions Age-related cataract is positively associated with skin cancer and its subtypes, including premalignant lesions in an older Australian population.Purpose The functional interaction between photoreceptors and retinal pigment epithelium (RPE) cells is essential for vision. Phagocytosis of photoreceptor outer segments (POSs) by the RPE follows a circadian pattern; however, it remains unknown whether other RPE processes follow a daily rhythm. Therefore, our aim was to identify RPE processes following a daily rhythm. Methods Murine RPE was isolated at Zeitgeber time (ZT) 0, 2, 4, 9, 14, and 19 (n = 5 per time point), after which RNA was isolated and sequenced. Genes with a significant difference in expression between time points (P less then 0.05) were subjected to EnrichR pathway analysis to identify daily rhythmic processes. selleck chemicals Results Pathway enrichment revealed 13 significantly enriched KEGG pathways (P less then 0.01), including the metabolic pathway (P = 0.002821). Analysis of the metabolic pathway differentially expressed genes revealed that genes involved in adenosine triphosphate production, glycolysis, glycogenolysis, and glycerophospholipid were low at ZT0 (light onset) and high at ZT19 (night). Genes involved in fatty acid degradation and cholesterol synthesis were high at light onset and low at night. Conclusions Our transcriptome data suggest that the highest energy demand of RPE cells is at night, whereas POS phagocytosis and degradation take place in the morning. Furthermore, we identified genes involved in fatty acid and glycerophospholipid synthesis that are upregulated at night, possibly playing a role in generating building blocks for membrane synthesis.Purpose To determine the effect of voluntary exercise on choroidal neovascularization (CNV) in mice. Methods Age-matched wild-type C57BL/6J mice were housed in cages equipped with or without running wheels. After four weeks of voluntary running or sedentariness, mice were subjected to laser injury to induce CNV. After surgical recovery, mice were placed back in cages with or without exercise wheels for seven days. CNV lesion volumes were measured by confocal microscopy. The effect of wheel running only in the seven days after injury was also evaluated. Macrophage abundance and cytokine expression were quantified. Results In the first study, exercise-trained mice exhibited a 45% reduction in CNV volume compared to sedentary mice. In the replication study, a 32% reduction in CNV volume in exercise-trained mice was observed (P = 0.029). Combining these two studies, voluntary exercise was found to reduce CNV by 41% (P = 0.0005). Exercise-trained male and female mice had similar CNV volumes (P = 0.99). The daily running distance did not correlate with CNV lesion size.
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