Baicalein-A Potent Pro-Homeostatic Regulator of Microglia in Retinal Ischemic Injury.

Retinal ischemia is a common cause of many retinal diseases, leading to irreversible vision impairment and blindness. Excessive neuroinflammation, including microglial activation and T-cell responses, has been identified as a critical factor associated with neurodegeneration in retinal ischemia. Baicalein is a natural flavonoid reported to have broad anti-inflammatory and neuroprotective bioactivities. Herein, the effects of baicalein on microglia activation in vitro and in vivo were investigated. We found that baicalein exhibited robust anti-inflammatory effect on cultured human and mouse microglia, as demonstrated by decreased induction of pro-inflammatory cytokines and the phosphorylation of phosphoinositide 3-kinase (PI3K) and nuclear factor kappa B (NFκB). Proteomic analysis further unraveled baicalein's effect on modulating IL-17 signaling pathways and its upstream regulator IL-1ß. Intravitreal administration of baicalein in the mouse model of retinal ischemia/reperfusion (I/R) injury attenuated microglial activation and retinal T-cell infiltration, particularly the T helper 17 cells. Additionally, baicalein was shown to exert neuroprotective effects by significantly reducing the retinal ganglion cell (RGC) loss after I/R injury, leading to an improved retinal function and spatial vision. These results suggest that baicalein, a natural flavonoid, acts as a negative regulator of activated microglia and immune responses both in vitro and in vivo, effectively alleviating neurodegeneration in retinal I/R injury. This finding indicates that baicalein could be a potential therapeutic agent against currently incurable degenerative retinal diseases.

Quantitative profiling of regional protein expression in rat retina after partial optic nerve transection using fluorescence difference two­dimensional gel electrophoresis.

To examine the difference between primary and secondary retinal ganglion cell (RGC) degeneration, the protein expression at four regions of retina including superior, temporal, inferior and nasal quadrant in a rat model of partial optic nerve transection (pONT) using 2­D Fluorescence Difference Gel Electrophoresis (DIGE) were investigated. Unilateral pONT was performed on the temporal side of optic nerves of adult Wistar rats to separate primary and secondary RGC loss. Topographical quantification of RGCs labeled by Rbpms antibody and analysis of axonal injury by grading of optic nerve damage at 1 week (n=8) and 8 weeks (n=15) after pONT demonstrated early RGC loss at temporal region, which is considered as primary RGC degeneration and progressing RGC loss at nasal region, which is considered as secondary RGC degeneration. Early protein expression in each retinal quadrant (n=4) at 2 weeks after pONT was compared with the corresponding quadrant in the contralateral control eye by DIGE. For all comparisons, 24 differentially expressed proteins (>1.2­fold; P<0.05; ≥3 non­duplicated peptide matches) were identified by mass spectrometry (MS). Interestingly, in the nasal retina, serum albumin and members of crystallin family, including αA, αB, ßA2, ßA3, ßB2 and gamma S indicating stress response were upregulated. By contrast, only αB and ßA2 crystallin proteins were altered in temporal quadrant. In the superior and inferior quadrants, ßB2 crystallin, keratin type I, S­arrestin and lamin­B1 were upregulated, while heat shock cognate 71 kDa protein and heterogeneous nuclear ribonucleoproteins A2/B1 were downregulated. In summary, the use of DIGE followed by MS is useful to detect early regional protein regulation in the retina after localized optic nerve injury.

Early quantitative profiling of differential retinal protein expression in lens-induced myopia in guinea pig using fluorescence difference two-dimensional gel electrophoresis.

The current study aimed to investigate the differential protein expression in guinea pig retinas in response to lens-induced myopia (LIM) before fully compensated eye growth. Four days old guinea pigs (n=5) were subjected to ­4D LIM for 8 days. Refractive errors were measured before and at the end of the lens wear period. Ocular dimensions were also recorded using high­frequency A­scan ultrasonography. After the LIM treatment, retinas of both eyes were harvested and soluble proteins were extracted. Paired retinal protein expressions in each animal were profiled and compared using a sensitive fluorescence difference two­dimensional gel electrophoresis. The quantitative retinal proteomes of myopic and control eye were analysed using computerised DeCyder software. Those proteins that were consistently changed with at least 1.2­fold difference (P<0.05) in the same direction in all five animals were extracted, trypsin digested and identified by tandem mass spectrometry. Significant myopia was induced in guinea pigs after 8 days of lens wear. The vitreous chamber depth in lens­treated eyes was found to be significantly elongated. Typically, more than 1,000 protein spots could be detected from each retina. Thirty­two of them showed differential expression between myopic and untreated retina. Among these proteins, 21 spots were upregulated and 11 were downregulated. Eight protein spots could be successfully identified which included ß­actin, enolase 1, cytosolic malate dehydrogenase, Ras­related protein Rab­11B, protein­L­isoaspartate (D­aspartate) O­methyltransferase, PKM2 protein, X­linked eukaryotic translation initiation factor 1A and ACP1 protein. The present study serves as the first report to uncover the retinal 2D proteome expressions in mammalian guinea pig myopia model using a top­down fluorescent dyes labelling gel approach. The results showed a downregulation in glycolytic enzymes that may suggest a significant alteration of glycolysis during myopia development. Other protein candidates also suggested multiple pathways which could provide new insights for further study of the myopic eye growth.

Optical Defocus Rapidly Changes Choroidal Thickness in Schoolchildren.

The current study aimed to examine the short-term choroidal response to optical defocus in schoolchildren. Myopic schoolchildren aged 8-16 were randomly allocated to control group (CG), myopic defocus group (MDG) and hyperopic defocus group (HDG) (n = 17 per group). Children in MDG and HDG received additional +3D and -3D lenses, respectively, to their full corrections on the right eyes. Full correction was given to their left eyes, and on both eyes in the CG. Axial length (AXL) and subfoveal choroidal thickness (SFChT) were then measured by spectral domain optical coherence tomography. Children wore their group-specific correction for 2 hours after which any existing optical defocus was removed, and subjects wore full corrections for another 2 hours. Both the AXL and SFChT were recorded hourly for 4 hours. The mean refraction of all subjects was -3.41 ± 0.37D (± SEM). SFChT thinned when exposed to hyperopic defocus for 2 hours but less thinning was observed in response to myopic defocus compared to the control group (p < 0.05, two-way ANOVA). Removal of optical defocus significantly decreased SFChT in the MDG and significantly increased SFChT in the HDG after 1 and 2 hours (mean percentage change at 2-hour; control vs. hyperopic defocus vs. myopic defocus; -0.33 ± 0.59% vs. 3.04 ± 0.60% vs. -1.34 ± 0.74%, p < 0.01). Our results showed short-term exposure to myopic defocus induced relative choroidal thickening while hyperopic defocus led to choroidal thinning in children. This rapid and reversible choroidal response may be an important clinical parameter in gauging retinal response to optical defocus in human myopia.

Impact on obesity-related illnesses and quality of life following intragastric balloon.

BACKGROUND: The impact of intragastric balloon (IGB) on obesity-related illnesses and quality of life (QOL) has not been previously investigated. METHOD: One hundred and nineteen consecutive obese patients (86 females; mean age 37.8; mean body weight (BW) 103.7 +/- 24.1 kg; mean BMI 38.4 +/- 8.0 kg/m(2)) who underwent IGB were evaluated for improvement on obesity-related illnesses and QOL after weight reduction in a multidisciplinary university referral center. Bioenterics Intragastric balloon (BIB system was employed in the study. RESULTS: Mean treatment period was 169.9 +/- 34.8 days. Mean BW, BMI, and excess body weight loss were 12.4 +/- 6.9 kg, 4.6 +/- 2.7 kg/m(2), and 45.1 +/- 35.3%. Mean waist circumference and biceps fold and triceps fold loss were 10.5 +/- 8.3, 9.8 +/- 8.5, and 8.7 +/- 7.4 cm respectively. Metabolic syndrome was decreased from 42.9% to 15.1% after IGB (p < 0.0005). Improvement of obesity-related illnesses were significant in fasting glucose, cholesterol, triglyceride, C-reactive protein, and blood pressure (p < 0.005).In 28 diabetes patients, HBA1C level was significantly decreased as compared to baseline (7.4 vs. 5.8%; p < 0.0005). The QOL of patients was significantly improved after IGB (p < 0.05). No serious complication related to IGB was observed. Four patients (3.3%) had intolerance and required early removal of balloon. Thirty-one patients (26%) received further bariatric surgery after IGB. CONCLUSIONS: IGB produces meaningful weight loss and significantly improves obesity-related illnesses and quality of life.

Simultaneous defocus integration during refractive development.

PURPOSE: To determine the effects of simultaneously presented myopic and hyperopic defocus on the refractive development of chicks. METHODS: A novel form of dual-power lens was designed. Normal chicks 7 to 8 days of age were fitted with a dual-power lens over one eye and a plano lens over the fellow (control) eye. Dual-power lenses of +20/-10, +10/-10, +5/-10, and plano/-10-D were tested, along with +10/-10-D lenses having differing ratios (50:50, 33:67, and 25:75) of surface area devoted to each power. Ocular refraction and axial ocular component dimensions were assessed after 6 days of lens wear, by retinoscopy and high-frequency ultrasound, respectively. In a separate experiment designed to test the effect of dual-power lens wear on the refractive development of myopic eyes, chicks were fitted with a dual-power +10/-10-D lens for 6 days, after myopia had been induced by 6 days of -10-D lens wear. RESULTS: For each of the dual-power lenses tested, the refractive end point of the treated eye was found to lie between the two optical powers of the lens (but with the response weighted in favor of the effect of myopic defocus). Refractive development appeared to be modulated by the sign, dioptric magnitude, and relative contribution (relative contrast) of the imposed optical defocuses through an integrative mechanism. Chicks with myopia induced by -10-D lens wear recovered when treated with a +10/-10-D dual-power lens. CONCLUSIONS: The chick retina can discern both the sign and the magnitude of optical defocus. Chick eyes were able to integrate blur cues from simultaneously presented images focused either side of the photoreceptors and to modulate their refractive development accordingly. This implies that the complex nature of defocus in the visual environment may play a critical role in the pathogenesis of myopia. The results suggest a rational method for arresting or reversing the development of myopia, which may be useful in the treatment of human myopia if the primate retina is also capable of responding to simultaneously presented opposing defocus cues.

[Effectiveness and safety of intragastric balloon for treatment of morbid obesity].

OBJECTIVE: To evaluate the effectiveness and safety of intragastric balloon (IGB) for the treatment of obese Chinese. METHODS: IGB was placed into the stomachs of 48 Chinese patients in Hong Kong, 13 males and 35 females; aged 39 +/- 9 (18 - 65), with the mean baseline body weight (BW) of 106 +/- 26 kg and mean body mass index (BMI) of (40 +/- 9) kg/m(2), 34 (70.8%) with coexistent obesity-related morbidities, who failed to respond to other weight reducing treatment, via routine gastroscopy under intravenous conscious sedation. Restricted balanced diet with 1200 kcal/day and exercise of 150 minutes/week were prescribed after the balloon placement. The IGB was removed endoscopically after at most 180 days. Follow-up was conducted once a week during the first month and then once a month. RESULTS: The median hospital stay and treatment duration were 1 (IQR 1:2.25) day and 174 (IQR 166:181) days respectively. The BW, BMI, and waist circumference were significantly decreased after the IGB placement (all P < 0.01) with the mean BW loss of (13 +/- 7) kg, mean BMI loss of (5 +/- 3) kg/m(2), mean excessive body weight loss of (45 +/- 36)%, and mean waist circumference loss of (12 +/- 8) cm. 66.7% of the patients were satisfied with the treatment. No serious complication related to IGB was noted. CONCLUSION: IGB is a safe and effective device that achieves moderate weight loss in obese Chinese.

Intragastric balloon in ethnic obese Chinese: initial experience.

BACKGROUND: We evaluated the effectiveness and safety of intragastric balloon (IGB) for the treatment of obesity in ethnic Chinese in Hong Kong. METHODS: 15 Chinese patients (10 females; median age 40 years (range 21-58)) completed IGB treatment over a 10-month period since November 2004. Median baseline body weight (BW) and BMI were 100.1 (range 78.5-170.3) kg and 39.4 (range 29.6-56.9) kg/m2 respectively. Coexistent obesity-related morbidities were present in 80% of patients. The Bioenterics Intragastric Balloon (BIB) was employed, and all placement and removal were performed endoscopically under intravenous conscious sedation. A restricted balanced diet (approximately 1200 kcal/day) and 150 minutes/week of moderate-intensity exercise were prescribed after balloon placement in a multidisciplinary approach. Outcome measures were collected and assessed in a prospective manner. RESULTS: Median procedure time was 25 (range 19-45) minutes and median hospital stay was 2 (range 1-6) days. Median BW and BMI loss were 15.3 (range 5.3-30.9) kg and 5.6 (range 1.9-12.5) kg/m2 after IGB. The median waist circumference (WC) loss was 9 (range 4-23) cm, and 66.7% of patients were highly satisfied with the treatment. No serious complication related to IGB was observed. CONCLUSION: IGB is a safe and effective device that achieves moderate weight loss in obese ethnic Chinese patients.