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Keratoconus is a degenerative disorder with progressive stromal thinning and transformation of the normal corneal architecture towards ectasia that results in decreased vision due to irregular astigmatism and irreversible tissue scarring. The pathogenesis of keratoconus still remains unclear. Hypotheses that this condition has an inflammatory etiopathogenetic component apart from the genetic and environmental factors are beginning to escalate in the research domain. This paper covers the most relevant and recent published papers regarding the biomarkers of inflammation, their signaling pathway, and the potentially new therapeutic options in keratoconus.

Background Aging is a complex physiological phenomenon, intricately associated with cardiovascular pathologies, where platelets play a central pathophysiological role. Although antiplatelets are commonly employed to prevent and treat major adverse cardiovascular events, aging associated intraplatelet changes remain largely unexplored. Methods Platelets were studied in high cardiovascular risk patients (aged 40–100 years) comparing them to younger healthy subjects. This was followed by cross sectional and longitudinal mice studies. Flow cytometry, biochemical and molecular assays were used to study platelets comprehensively. Findings CVD Patients were categorized in the age groups 40–59, 60–79, and 80–100 years. Progressive decline in platelet health was observed in the 40–79 years age cohort, marked by increase in oxidative stress, hyperactivation and apoptotic markers. Paradoxically, this was reversed in patients aged above 79 years and the improved platelet phenotype was associated with lower oxidative damage. The platelets from the very old (80–100 year) group were found to be preloaded with increased antioxidants, which also contributed to higher resistance against induced redox insults. Cross sectional mouse studies excluded the effect of comorbidities and medications. Longitudinal mouse studies implicate an adaptive increase in antioxidant levels as the mechanism. Interpretation We report a novel age associated, non-linear redox regulation in platelets in both humans and mice. In advanced age, there occurs an adaptive increase in platelet antioxidants, reducing the intracellular ROS and leading to a healthier platelet phenotype. Clinically, our results advocate the use of less aggressive antiplatelet therapies for CVD in the elderly population. Fund Study funded by NIH-NHLBI, RO1-HL122815 and RO1-HL115247.

Mitophagy can selectively remove damaged toxic mitochondria, protecting a cell from apoptosis. The molecular spatial–temporal mechanisms governing autophagosomal selection of reactive oxygen species (ROS)‐damaged mitochondria, particularly in a platelet (no genomic DNA for transcriptional regulation), remain unclear. We now report that the mitochondrial matrix protein MsrB2 plays an important role in switching on mitophagy by reducing Parkin methionine oxidation (MetO), and transducing mitophagy through ubiquitination by Parkin and interacting with LC3. This biochemical signaling only occurs at damaged mitochondria where MsrB2 is released from the mitochondrial matrix. MsrB2 platelet‐specific knockout and in vivo peptide inhibition of the MsrB2/LC3 interaction lead to reduced mitophagy and increased platelet apoptosis. Pathophysiological importance is highlighted in human subjects, where increased MsrB2 expression in diabetes mellitus leads to increased platelet mitophagy, and in platelets from Parkinson's disease patients, where reduced MsrB2 expression is associated with reduced mitophagy. Moreover, Parkin mutations at Met192 are associated with Parkinson's disease, highlighting the structural sensitivity at the Met192 position. Release of the enzyme MsrB2 from damaged mitochondria, initiating autophagosome formation, represents a novel regulatory mechanism for oxidative stress‐induced mitophagy.

Background Drug‐coated balloon (DCB) angioplasty has emerged as a mainstay of therapy for the treatment of peripheral arterial disease (PAD) involving the superficial femoral and popliteal arteries. We performed a meta‐analysis including all available randomized controlled trials (RCTs) to date which compare DCB to plain balloon angioplasty (POBA) in femoropopliteal disease (FPD). Methods Five databases were analyzed including EMBASE, PubMed, Cochrane, Scopus, and Web‐of‐Science from January 2000 to September 2018 for RCTs comparing DCB to POBA in patients with FPD. Heterogeneity was determined using Cochrane's Q‐statistics. Random effects model was used. Results Twenty‐two RCTs, including five trials of in‐stent restenosis (ISR) intervention, with 3,217 patients were included in the analysis. Mean follow‐up was approximately 21.6 ± 14.4 months. Overall, DCB use was associated with a 51% reduction in target vessel revascularization (TLR) when compared to POBA at follow‐up (relative risk [RR]: 0.49, 95% confidence interval [CI]: 0.40–0.61, P < 0.0001). Rates of TLR were 45% lower in the DCB group when compared to POBA in patients with ISR (RR: 0.55, 95% CI: 0.37–0.81, P = 0.002). DCB was associated with lower rates of binary stenosis, late lumen loss and higher primary safety endpoints. Major amputation and mortality were not different between DCB and POBA. Conclusions Use of DCBs is associated with improved vessel patency and a lower risk of TLR when compared to POBA in patients with FPD, especially in the setting of ISR. There was no difference in mortality between DCB and POBA in our meta‐analysis. Extended follow‐up of the available RCT data will be essential to analyze long‐term device‐related mortality.