The Adenosine Receptor Antagonist, 7-Methylxanthine, Alters Emmetropizing Responses in Infant Macaques

PURPOSE. Previous studies suggest that the adenosine receptor antagonist, 7-methylxanthine (7-MX), retards myopia progression. Our aim was to determine whether 7-MX alters the compensating refractive changes produced by defocus in rhesus monkeys. METHODS. Starting at age 3 weeks, monkeys were reared with -3 diopter (D; n = 10; 7-MX -3D/pl) or +3D (n = 6; 7-MX +3D/pl) spectacles over their treated eyes and zero-powered lenses over their fellow eyes. In addition, they were given 100 mg/kg of 7-MX orally twice daily throughout the lens-rearing period (age 147±4 days). Comparison data were obtained from lens-reared controls (-3D/pl, n = 17; +3D/pl, n = 9) and normal monkeys (n = 37) maintained on a standard diet. Refractive status, corneal power, and axial dimensions were assessed biweekly. RESULTS. The -3D/pl and +3D/pl lens-reared controls developed compensating myopic (-2.10±1.07 D) and hyperopic anisometropias (+1.86±0.54 D), respectively. While the 7-MX +3D/pl monkeys developed hyperopic anisometropias (+1.79±1.11 D) that were similar to those observed in +3D/pl controls, the 7-MX -3D/pl animals did not consistently exhibit compensating myopia in their treated eyes and were on average isometropic (+0.35±1.96 D). The median refractive errors for both eyes of the 7-MX -3D/pl (+5.47 D and +4.38 D) and 7-MX +3D/pl (+5.28 and +3.84 D) monkeys were significantly more hyperopic than that for normal monkeys (+2.47 D). These 7-MX-induced hyperopic ametropias were associated with shorter vitreous chambers and thicker choroids. CONCLUSIONS. In primates, 7-MX reduced the axial myopia produced by hyperopic defocus, augmented hyperopic shifts in response to myopic defocus, and induced hyperopia in control eyes. The results suggest that 7-MX has therapeutic potential in efforts to slow myopia progression

Antioxidant Activities and GCMS Analysis of Anacardium occidentale L. Fruits

Anacardium occidentale belongs to the family Anacardiaceae is a tropical evergreen tree with spreading branches which are supported by aerial roots that go down into the soil to form the 'props'. The milky latex is applied externally for treating pains in rheumatism and in lumbago. The infusion of the bark is used against dysentery, diarrhoea and diabetes. The study aims to evaluate the antioxidant activities and GC-MS analysis of ethanol and aqueous fruit extracts of Anacardium occidentale. The antioxidant assays such as DPPH˙ radical, Superoxide (O2.‑) radical, ABTS●+ radical cation scavenging activities, phoshomolybdenum reduction and Fe3+ reduction activities were carried out for ethanol and aqueous fruit extracts. The maximum DPPH˙ radical scavenging activity for ethanol extract was 93.33±0.23 at 120 µg/mL concentration and the IC50 was 38.29 μg/mL concentration. The maximum superoxide (O2.‑) radical scavenging activity was 75±0.25 at 120 µg/mL concentration and the IC50 was 38.52 μg/mL concentration for ethanol extract. The maximum ABTS●+ radical cation scavenging activity for ethanol extract was 82.57±0.37 at 30 µg/mL concentration and the IC50 was 11.13 μg/mL concentration. The maximum phosphomolybdenum reduction was 92.94±0.19 at 120 µg/mL concentration and the RC50 was 17.75 μg/mL concentration for ethanol extract. The maximum Fe3+ reduction for ethanol extract was 75.99±0.31 at 120 µg/mL concentration and the RC50 was 40.48 μg/mL concentration. GC-MS analysis showed different ester derivative compounds present in the ethanol fruit extract of Anacardium occidentale exhibiting antioxidant, anti-inflammatory, antimicrobial activities. Keywords: Anacardium occidentale, DPPH˙ radical, Superoxide (O2.‑) radical, ABTS●+ radical cation GC-MS analysis

The Effects of the Relative Strength of Simultaneous Competing Defocus Signals on Emmetropization in Infant Rhesus Monkeys

PURPOSE. We investigated how the relative surface area devoted to the more positive-powered component in dual-focus lenses influences emmetropization in rhesus monkeys. CONCLUSIONS. The results demonstrate that even when the more positive-powered zones make up only one-fifth of a dual-focus lens' surface area, refractive development is still dominated by relative myopic defocus. Overall, the results emphasize that myopic defocus distributed across the visual field evokes strong signals to slow eye growth in primates

Myopia Control Dose Delivered to Treated Eyes by a Dual Focus Myopia Control Contact Lens

SIGNIFICANCE Consistent with closed-loop models of regulated eye growth, a successful dual-focus (DF) myopia-control contact lens focused a significant proportion of light anterior to the central retina in eyes of treated children viewing near and distant targets. PURPOSE This study examined the optical impact of a DF contact lens during near viewing in a sample of habitual DF lens wearing children. METHODS Seventeen myopic children aged 14 to 18 years who had completed 3 or 6 years of treatment with a DF contact lens (MiSight 1 Day; CooperVision, Inc., San Ramon, CA) were recruited and fit bilaterally with the DF and a single-vision (Proclear 1 Day; CooperVision, Inc.) contact lens. Right eye wavefronts were measured using a pyramidal aberrometer (Osiris; CSO, Florence, Italy) while children accommodated binocularly to high-contrast letter stimuli at five target vergences. Wavefront error data were used to compute pupil maps of refractive state. RESULTS During near viewing, children wearing single-vision lenses accommodated on average to achieve approximate focus in the pupil center but, because of combined accommodative lag and negative spherical aberration, experienced up to 2.00 D of hyperopic defocus in the pupil margins. With DF lenses, children accommodated similarly achieving approximate focus in the pupil center. When viewing three near distances (0.48, 0.31, and 0.23 m), the added +2.00 D within the DF lens treatment optics shifted the mean defocus from +0.75 to -1.00 D. The DF lens reduced the percentage of hyperopic defocus (≥+0.75 D) in the retinal image from 52 to 25% over these target distances, leading to an increase in myopic defocus (≤-0.50 D) from 17 to 42%. CONCLUSIONS The DF contact lens did not alter the accommodative behavior of children. The treatment optics introduced myopic defocus and decreased the amount of hyperopically defocused light in the retinal image

Immunotoxin-Induced Ablation of the Intrinsically Photosensitive Retinal Ganglion Cells in Rhesus Monkeys

Purpose: Intrinsically photosensitive retinal ganglion cells (ipRGCs) contain the photopigment melanopsin, and are primarily involved in non-image forming functions, such as the pupillary light reflex and circadian rhythm entrainment. The goal of this study was to develop and validate a targeted ipRGC immunotoxin to ultimately examine the role of ipRGCs in macaque monkeys.Methods: An immunotoxin for the macaque melanopsin gene (OPN4), consisting of a saporin-conjugated antibody directed at the N-terminus, was prepared in solutions of 0.316, 1, 3.16, 10, and 50 μg in vehicle, and delivered intravitreally to the right eye of six rhesus monkeys, respectively. Left eyes were injected with vehicle only. The pupillary light reflex (PLR), the ipRGC-driven post illumination pupil response (PIPR), and electroretinograms (ERGs) were recorded before and after injection. For pupil measurements, 1 and 5 s pulses of light were presented to the dilated right eye while the left pupil was imaged. Stimulation included 651 nm (133 cd/m2), and 4 intensities of 456 nm (16–500 cd/m2) light. Maximum pupil constriction and the 6 s PIPR were calculated. Retinal imaging was performed with optical coherence tomography (OCT), and eyes underwent OPN4 immunohistochemistry to evaluate immunotoxin specificity and ipRGC loss.Results: Before injection, animals showed robust pupil responses to 1 and 5 s blue light. After injection, baseline pupil size increased 12 ± 17%, maximum pupil constriction decreased, and the PIPR, a marker of ipRGC activity, was eliminated in all but the lowest immunotoxin concentration. For the highest concentrations, some inflammation and structural changes were observed with OCT, while eyes injected with lower concentrations appeared normal. ERG responses showed better preserved retinal function with lower concentrations. Immunohistochemistry showed 80–100% ipRGC elimination with the higher doses being more effective; however this could be partly due to inflammation that occurred at the higher concentrations.Conclusion: Findings demonstrated that the OPN4 macaque immunotoxin was specific for ipRGCs, and induced a graded reduction in the PLR, as well as, in ipRGC-driven pupil response with concentration. Further investigation of the effects of ipRGC ablation on ocular and systemic circadian rhythms and the pupil in rhesus monkeys will provide a better understanding of the role of ipRGCs in primates

Long-term Effect of Dual-focus Contact Lenses on Myopia Progression in Children: A 6-year Multicenter Clinical Trial

SIGNIFICANCE Treatment of myopic children with a dual-focus soft contact lens (DFCL; MiSight 1 day) produced sustained slowing of myopia progression over a 6-year period. Significant slowing was also observed in children switched from a single vision control to treatment lenses (3 years in each lens). PURPOSE This study aimed to evaluate the effectiveness of DFCLs in sustaining slowed progression of juvenile-onset myopia over a 6-year treatment period and assess myopia progression in children who were switched to a DFCL at the end of year 3. METHODS Part 1 was a 3-year clinical trial comparing DFCLs with a control contact lens (Proclear 1 day) at four investigational sites. In part 2, subjects completing part 1 were invited to continue for 3 additional years during which all children were treated with MiSight 1 day DFCLs (52 and 56 from the initially treated [T6] and control [T3] groups, respectively). Eighty-five subjects (45 [T3] and 40 [T6]) completed part 2. Cyclopleged spherical equivalent refractive errors (SEREs) and axial lengths (ALs) were monitored, and a linear mixed model was used to compare their adjusted change annually. RESULTS Average ages at part 2 baseline were 13.2 ± 1.3 and 13.0 ± 1.5 years for the T6 and T3 groups, respectively. Slowed myopia progression in the T6 group observed during part 1 was sustained throughout part 2 (mean ± standard error of the mean: change from baseline SERE [in diopters], -0.52 ± 0.076 vs. -0.51 ± 0.076; change in AL [in millimeters], 0.28 ± 0.033 vs. 0.23 ± 0.033; both P >.05). Comparing progression rates in part 2 for the T6 and T3 groups, respectively, indicates that prior treatment does not influence efficacy (SERE, -0.51 ± 0.076 vs. -0.34 ± 0.077; AL, 0.23 ± 0.03 vs. 0.18 ± 0.03; both P >.05). Within-eye comparisons of AL growth revealed a 71% slowing for the T3 group (3 years older than part 1) and further revealed a small subset of eyes (10%) that did not respond to treatment. CONCLUSIONS Dual-focus soft contact lenses continue to slow the progression of myopia in children over a 6-year period revealing an accumulation of treatment effect. Eye growth of the initial control cohort with DFCL was slowed by 71% over the subsequent 3-year treatment period

Micropropagation and conservation of selected endangered anticancer medicinal plants from the Western Ghats of India

Globally, cancer is a constant battle which severely affects the human population. The major limitations of the anticancer drugs are the deleterious side effects on the quality of life. Plants play a vital role in curing many diseases with minimal or no side effects. Phytocompounds derived from various medicinal plants serve as the best source of drugs to treat cancer. The global demand for phytomedicines is mostly reached by the medicinal herbs from the tropical nations of the world even though many plant species are threatened with extinction. India is one of the mega diverse countries of the world due to its ecological habitats, latitudinal variation, and diverse climatic range. Western Ghats of India is one of the most important depositories of endemic herbs. It is found along the stretch of south western part of India and constitutes rain forest with more than 4000 diverse medicinal plant species. In recent times, many of these therapeutically valued herbs have become endangered and are being included under the red-listed plant category in this region. Due to a sharp rise in the demand for plant-based products, this rich collection is diminishing at an alarming rate that eventually triggered dangerous to biodiversity. Thus, conservation of the endangered medicinal plants has become a matter of importance. The conservation by using only in situ approaches may not be sufficient enough to safeguard such a huge bio-resource of endangered medicinal plants. Hence, the use of biotechnological methods would be vital to complement the ex vitro protection programs and help to reestablish endangered plant species. In this backdrop, the key tools of biotechnology that could assist plant conservation were developed in terms of in vitro regeneration, seed banking, DNA storage, pollen storage, germplasm storage, gene bank (field gene banking), tissue bank, and cryopreservation. In this chapter, an attempt has been made to critically review major endangered medicinal plants that possess anticancer compounds and their conservation aspects by integrating various biotechnological tool

Strategies to inhibit myopia: pharmacological and optical approaches

© 2011 Dr. Baskar ArumugamAims: Myopia is a significant public health issue affecting around 30% of the world’s population and is a major cause of blindness because of the increased risk of pathology to the retina, choroid and sclera. Currently there is no effective treatment for myopia. The broadband muscarinic antagonist agent atropine and the M1/M4 receptor selective muscarinic antagonist pirenzepine are effective at slowing the progression of myopia in animals and humans. However, uncertainty remains as to whether this effect occurs through a receptoral mechanism and, if so, which muscarinic receptor mediates this effect. An optical strategy that has been investigated in recent times is the effect of intermittent positive lens wear to reduce myopia progression. This thesis conducts a series of investigations on animal models of myopia to further assess both pharmacological and optical strategies to inhibit myopia. Methods: The animal models used for these investigations were chicks and tree shrews. Chicks underwent daily intravitreal injections with MT3 or MT7 or MT3 + spiperone for four consecutive days in the treated eye. The contralateral control eye was untreated and used for comparison. After the treatment period, keratometry, retinoscopy and A-Scan ultrasound were used to assess ocular biometry. Tree shrews underwent daily intravitreal injections with MT3 or MT7 or saline vehicle for five consecutive days in the treated eye and form-deprivation. The contralateral control eyes underwent intravitreal injections of saline and were unoccluded for the same period. Two more of tree shrew groups underwent daily intravitreal injections with MT7 or saline vehicle for ten consecutive days in the treated eye combined with negative lens defocus. The control eye was injected with saline and wore plano lenses for 10 days. The optical and structural measurements were taken before the start of treatment and after the treatment. In a study to assess intermittent positive lens wear on experimentally induced myopia, tree shrews wore binocular -9.5D lenses. The negative lens defocus was either never interrupted or interrupted twice daily with binocular positive (+4.0D) or plano lens wear for twelve days. The optical and structural measurements were performed before the start of treatment, 5 and 12 days. Results: MT3 treatment produced a significant dose-dependent reduction in relative myopia in chicks compared to vehicle (treated – control eye; vehicle -10.1 ± 1.1D; 10µM MT3; -4.0 ± 1.5D; p<0.01). The majority of this effect was due the inhibition of vitreous chamber depth (treated – control eye; vehicle; 0.26 ± 0.04 mm vs 10µM MT3; 0.08 ± 0.07 mm, p<0.05). The relative combined retina + choroid thickness was significantly different between MT3 and vehicle groups (treated – control eye; vehicle; -0.19 ± 0.03 mm vs 10µM MT3; 0.02 ± 0.05 mm; p<0.01). MT7 had no significant effect on the development of myopia in chicks, relative to vehicle control. In tree shrew, both MT3 and MT7 prevented the form-deprivation myopia (treated – control eye; myopia; vehicle; -4.3 ± 0.6D vs MT3; -0.7 ± 0.2D and MT7; -0.7 ± 0.4D; p<0.001). The MT7 treatment was also effective in inhibiting the lens-induced myopia (treated – control eye; vehicle; -4.6 ± 0.5D vs MT7; 0.2 ± 0.2D; p<0.05) and elongation of vitreous chamber depth (treated – control eye; vehicle; 0.07 ± 0.01 mm and MT7; 0.01 ± 0.02 mm; p<0.05). The co-application of MT3 + the D2 antagonist spiperone prevented MT3 inhibition of myopia (treated – control eye; MT3 + spiperone; -11.2 ± 1.2D vs MT3; -4.7 ± 1.2D; p<0.001). Intermittent binocular positive lens wear was significantly more effective in inhibiting negative lens induced myopia than binocular plano lens wear following 12 days (-9.5D / 0D (2); 6.8 ± 0.6D vs -9.5D / +4.0D (2); 9.5 ± 0.6D, p<0.05). Conclusions: The M4 muscarinic antagonist MT3 was effective at reducing myopia in chicks. Based on changes in choroidal thickness, it is proposed the site of action for MT3 inhibition occurs in the retina or choroid. Both the M4 and M1 receptors are implicated in the muscarinic antagonist inhibition of myopia in tree shrews. Antagonism of the D2 receptor demonstrated that dopaminergic signalling is involved in M4 muscarinic antagonist control of myopia in chicks. Intermittent binocular transient positive lens wear for only 4% of the day was more effective in reducing the binocular negative lens-induced myopia than transient plano lens wear in a tree shrew

Experimental Analysis on Tribological Behavior of Nano Based Bio-Lubricants using Four Ball Tribometer

The present work describes the tribological behavior of CuO, WS2 and TiO2 nano particles as an antiwear additive to a chemically modified rapeseed oil (CMRO). The tribological tests were run on a four ball tribometer. The variation of viscosity of various nano based biolubricants with respect to temperature is also estimated in accordance with ASTM D 445. The test results were compared with petroleum based synthetic lubricant (SAE20W40). The test results exhibited that CMRO with nano CuO has better tribological characteristics, smoother wear scar and higher viscosity compared to synthetic lubricant and other nano based biolubricants