The biophysical property of the limbal niche maintains stemness through YAP.

The cell fate decisions of stem cells (SCs) largely depend on signals from their microenvironment (niche). However, very little is known about how biochemical niche cues control cell behavior in vivo. To address this question, we focused on the corneal epithelial SC model in which the SC niche, known as the limbus, is spatially segregated from the differentiation compartment. We report that the unique biomechanical property of the limbus supports the nuclear localization and function of Yes-associated protein (YAP), a putative mediator of the mechanotransduction pathway. Perturbation of tissue stiffness or YAP activity affects SC function as well as tissue integrity under homeostasis and significantly inhibited the regeneration of the SC population following SC depletion. In vitro experiments revealed that substrates with the rigidity of the corneal differentiation compartment inhibit nuclear YAP localization and induce differentiation, a mechanism that is mediated by the TGFß-SMAD2/3 pathway. Taken together, these results indicate that SC sense biomechanical niche signals and that manipulation of mechano-sensory machinery or its downstream biochemical output may bear fruits in SC expansion for regenerative therapy.

Neovascular Glaucoma as a Presenting Sign of Catastrophic Antiphospholipid Syndrome with a "Catastrophic" Heart Valve Finding.

We aimed to describe a case of neovascular glaucoma (NVG) as a first presenting sign of catastrophic antiphospholipid syndrome (CAPS) with heart valve aseptic vegetations known as Libman-Sacks endocarditis. A 39-year-old man was referred for left eye decreased visual acuity and pain, upon examination left eye high intraocular pressure; rubeosis iridis of both eyes (BE); and prominent retinal ischemia. Clinical and fluorescein angiography findings established the diagnosis of left eye NVG with vaso-occlusive disease in BE. Magnetic resonance imaging of the head showed widespread ischemic lesions and hemorrhagic foci. The transesophageal echocardiogram showed 2 big mitral valve lesions consistent with the diagnosis of Libman-Sacks endocarditis. Laboratory and clinical diagnosis of CAPS and suspected SLE was confirmed, and treatment with anticoagulants and IV steroids was initiated. This case demonstrates that severe vaso-occlusive retinopathy with severe brain ischemia should raise the suspicion of systemic autoimmune pro-coagulative diseases with heart valve aseptic vegetations.

Glycemic Control and Quality of Life Following Cataract Surgery in Patients with Type 2 Diabetes and without Maculopathy.

OBJECTIVE: To assess whether cataract removal surgery will improve glycemic control and quality of life in patients with diabetes. METHODS: A prospective longitudinal study of 28 patients with type 2 diabetes and without diabetic retinopathy scheduled for cataract removal surgery. During the 4 months of follow-up, measurements of glycated hemoglobin (HbA1c) were obtained and assessment of quality of life was performed using two questionnaires: The EuroQoL 5-Dimension (EQ-5D®) and the Multidimensional Diabetes Questionnaire (MDQ). RESULTS: HbA1c values decreased by approximately 0.45% following surgery (7.24% to 6.78%, P = 0.009). Younger patients reduced HbA1c significantly more than older patients (0.73% vs. 0.03%, respectively, P = 0.043). Younger age also correlated with better visual acuity improvement (R = -0.44, P = 0.02). Poor glycemic control prior to surgery correlated with better HbA1c reductions, with a 42% chance for reduction of at least 0.5% HbA1c in patients with preoperative HbA1c values of 7.5% and a 72% chance for reduction in patients with preoperative HbA1c values of 8.5%. Quality of life was improved by 14% following surgery, as noted in the MDQ results (33.9-38.7, P = 0.034) only. CONCLUSIONS: Cataract removal surgery may positively influence glycemic control and quality of life in type 2 diabetic patients without maculopathy. Younger patients achieved superior improvement in visual and glycemic outcomes. The results of this study highlight the need for frequent inquiry regarding eyesight deterioration in patients with diabetes.

Treatment of retinal artery occlusion using transluminal Nd:YAG laser: a systematic review and meta-analysis.

AIMS: To review clinical experience, efficacy, and safety of transluminal Nd:YAG laser embolectomy/embolysis (TYE) for retinal artery occlusion. METHODS:  Electronic databases were searched for all published clinical studies and case-reports reporting on TYE in central (CRAO) or branch (BRAO) retinal artery occlusion. Individual patient data was evaluated in a weighted pooled analysis. RESULTS: Sixty-one cases were reported, 47 with BRAO and 14 with CRAO. Visual acuity (VA) at onset averaged 20/252 (1.1 LogMAR) and improved following the procedure to 20/47 (0.37 LogMAR) at first follow-up (avg. 6 days, P < 0.001) and to 20/30 (0.18 LogMAR) at last reported follow-up (avg. 1.1 years, P = 0.02). Patients with worse VA (<20/200) improved further (12 vs. three lines, P < 0.001). VA was not improved when using higher pulse energies (≥ 2.4 mJ) which were associated with more vitrectomies. In a weighted analysis vitreous/sub-retinal hemorrhage was estimated to occur in 54% of cases and required vitrectomy in 18% of cases. CONCLUSIONS: TYE was followed by significant visual improvement in the vast majority of cases, including CRAO, and was frequently associated with vitreous hemorrhage. Patients with poor visual acuity appear to benefit further and higher pulse energies may be detrimental. Lack of randomization and intrinsic biases prevent any definite conclusions regarding the benefits and further research is warranted.

Should Bilateral Internal Thoracic Artery Grafting Be Used in Patients After Recent Myocardial Infarction?

BACKGROUND: Bilateral internal thoracic artery grafting (BITA) is associated with improved survival. However, surgeons do not commonly use BITA in patients after myocardial infarction (MI) because survival is good with single internal thoracic artery grafting (SITA). We aimed to compare the outcomes of BITA with those of SITA and other approaches in patients with multivessel disease after recent MI. METHODS AND RESULTS: In total, 938 patients with recent MI (<3 months) who underwent BITA between 1996 and 2011 were compared with 682 who underwent SITA. SITA patients were older and more likely to have comorbidities (diabetes mellitus, chronic obstructive pulmonary disease, chronic renal failure, peripheral vascular disease), to be female, and to have had a previous MI. Acute MI and 3-vessel disease were more prevalent in the BITA group. Operative mortality of BITA patients was lower (3.0% versus 5.8%, P=0.01), and sternal infections and strokes were similar. Median follow-up was 15.21 years (range: 0-21.25 years). Survival of BITA patients was better (70.3% versus 52.5%, P<0.001). Propensity score matching was used to account for differences in preoperative characteristics between groups. Overall, 551 matched pairs had similar preoperative characteristics. BITA was a predictor of better survival in the matched groups (hazard ratio: 0.679; P=0.002; Cox model). Adjusted survival of emergency BITA and SITA patients was similar (hazard ratio: 0.883; P=0.447); however, in the nonemergency group, BITA was a predictor of better survival (hazard ratio: 0.790; P=0.009; Cox model). CONCLUSIONS: This study suggests that survival is better with BITA compared with SITA in nonemergency cases after recent MI, with proper patient selection.